Matches in Nanopublications for { ?s <http://www.w3.org/ns/prov#value> ?o ?g. }
- _3 value "il4, il12, and il18" provenance.
- _5 value "il4, il12, and il18" provenance.
- _3 value "platelet factor-4" provenance.
- _3 value "pleiotrophin" provenance.
- _3 value "proliferin-related protein" provenance.
- _2 value "tetrahydrocortisol-s" provenance.
- _4 value "this action is mediated through the induction of expression of the antiapoptotic proteins BCL2 and BCL-A1, regulation of PI3K/AKT pathway, increased phosphorylation of focal adhesion kinase, and stimulation of endothelial cell production of NO and prostaglandin I2" provenance.
- _5 value "this action is mediated through the induction of expression of the antiapoptotic proteins BCL2 and BCL-A1, regulation of PI3K/AKT pathway, increased phosphorylation of focal adhesion kinase, and stimulation of endothelial cell production of NO and prostaglandin I2" provenance.
- _3 value "thrombospondin-1" provenance.
- _5 value "In Sdc2 the central portion of the cytoplasmic domain is known to be phosphorylated on serines 197 and 198 by PKC doesn't affect dimer formation" provenance.
- _5 value "PMA-induction of Lkn-1/CCL15 in transiently transfected U937 cells was blocked by proteasome inhibitor 1. These observations demonstrate that the two NF-kappaB binding sites are essential for PMA-induced Lkn-1/CCL15 expression in human monocytes." provenance.
- _4 value "Furthermore, NF-kappaB and AP-1 control the expression of urokinase-type plasminogen activator (uPA) and its receptor (uPAR), and expression of both uPA and uPAR correlates with invasive cancer cell phenotype and poor prognosis. The inhibition of PKC and PI3K signaling (through NF-kappaB and AP-1) suppressed the secretion of uPA, resulting in the inhibition of motility of highly invasive breast cancer cells." provenance.
- _4 value "In addition, overexpression of HER3 and HER4 was also reported in breast cancers [83], and heregulin, which binds to HER3 and HER4 receptors, stimulated cell motility and upregulated the expression of uPA and uPAR [89]." provenance.
- _4 value "Increased expression of PKC in malignant and aggressive breast cancers was recently demonstrated, and PKC activity has been shown to be higher in breast cancers than in normal breast tissue [68, 69]. In addition, high levels of PKC? and -? were correlated with enhanced uPA secretion in highly invasive MDA-MB- 231 breast cancer cells [70]. Furthermore, the introduction of PKC? gene to nonmetastatic MCF-7 breast cancer cells resulted in more aggressive neoplastic phenotype, and the stimulation of PKC activity with phorbol ester, phorbol-12- myristate-13-acetate (PMA), resulted in increases in both invasiveness and uPA expression" provenance.
- _5 value "Increased expression of PKC in malignant and aggressive breast cancers was recently demonstrated, and PKC activity has been shown to be higher in breast cancers than in normal breast tissue [68, 69]. In addition, high levels of PKC? and -? were correlated with enhanced uPA secretion in highly invasive MDA-MB- 231 breast cancer cells [70]. Furthermore, the introduction of PKC? gene to nonmetastatic MCF-7 breast cancer cells resulted in more aggressive neoplastic phenotype, and the stimulation of PKC activity with phorbol ester, phorbol-12- myristate-13-acetate (PMA), resulted in increases in both invasiveness and uPA expression" provenance.
- _6 value "Several types of proteolytic enzymes have been identified to specifically degrade the proteins of the extracellular matrix: matrix metalloproteinases (MMPs) [5], cysteine proteases [6], and serine proteases [7]. Serine protease urokinase-type plasminogen activator (uPA) is a protease that cleaves the extracellular matrix and stimulates the conversion of plasminogen to plasmin [8]. Plasmin mediates invasion directly, by degrading matrix proteins such as collagen IV, fibronectin, and laminin, or indirectly, by activating matrix metalloproteinases MMP-2, -3, and -9 and serine protease uPA [9-12]. uPA exerts its nonproteolytic activity through its interaction with uPA receptor (uPAR), which forms the complex with integrins and controls cell adhesion and cell migration [" provenance.
- _3 value "Increased levels of GP73 expression were also noted in chronic HCV infection and alcoholic liver disease." provenance.
- _2 value "cadmium induces Hep3B cells apoptosis mainly by calcium- and oxidative stress-related impairment of mitochondria, which probably favors release of apoptosis-inducing factor and endonuclease G." provenance.
- _3 value "Overexpressing VACM-1 significantly attenuated cellular proliferation and MAPK phosphorylation when compared to the control cells. In addition, VACM-1 decreased egr-1 and increased Fas-L mRNA levels. Further, egr-1 protein levels were significantly lower in the nuclear fraction from VACM-1 transfected cells when compared to controls." provenance.
- _8 value "Contrary to the corepressors, the p160 NR coactivators bind to liganded NRs to mediate transcriptional activation through recruitment of histone acetyltransferases (10). The p160 coactivators include SRC-1 (11), GRIP1/TIF2 (12-14), and RAC3/ACTR/AIB1/pCIP/TRAM-1 (15-19). These coactivators also interact with histone acetyltransferases such as CREB-binding protein/p300 and P/CAF (22,23), tethering histone acetyltransferase activity to target promoters." provenance.
- _6 value "Contrary to the corepressors, the p160 NR coactivators bind to liganded NRs to mediate transcriptional activation through recruitment of histone acetyltransferases (10). The p160 coactivators include SRC-1 (11), GRIP1/TIF2 (12-14), and RAC3/ACTR/AIB1/pCIP/TRAM-1 (15-19). These coactivators also interact with histone acetyltransferases such as CREB-binding protein/p300 and P/CAF (22,23), tethering histone acetyltransferase activity to target promoters." provenance.
- _6 value "Contrary to the corepressors, the p160 NR coactivators bind to liganded NRs to mediate transcriptional activation through recruitment of histone acetyltransferases (10). The p160 coactivators include SRC-1 (11), GRIP1/TIF2 (12-14), and RAC3/ACTR/AIB1/pCIP/TRAM-1 (15-19). These coactivators also interact with histone acetyltransferases such as CREB-binding protein/p300 and P/CAF (22,23), tethering histone acetyltransferase activity to target promoters." provenance.
- _7 value "We found that ANCO-1 and likely its related protein ANCO-2 may represent a novel class of nuclear receptor corepressors that may inhibit transcriptional activity of NRs through interfering with the coactivator function of p160 by recruiting HDACs. We found that both ANCO-1C and the ANCO-1Ct fragment (amino acids 2597-2663) bound strongly to the full-length RAC3, TIF2, and SRC-1 (Fig. 1C)." provenance.
- _5 value "We found that ANCO-1 and likely its related protein ANCO-2 may represent a novel class of nuclear receptor corepressors that may inhibit transcriptional activity of NRs through interfering with the coactivator function of p160 by recruiting HDACs. We found that both ANCO-1C and the ANCO-1Ct fragment (amino acids 2597-2663) bound strongly to the full-length RAC3, TIF2, and SRC-1 (Fig. 1C)." provenance.
- _5 value "We found that ANCO-1 and likely its related protein ANCO-2 may represent a novel class of nuclear receptor corepressors that may inhibit transcriptional activity of NRs through interfering with the coactivator function of p160 by recruiting HDACs. We found that both ANCO-1C and the ANCO-1Ct fragment (amino acids 2597-2663) bound strongly to the full-length RAC3, TIF2, and SRC-1 (Fig. 1C)." provenance.
- _5 value "We found that ANCO-1 overexpression resulted in a concentration-dependent inhibition of ligand-induced transactivation by several NRs, including those for mineralocorticoid, androgen, progesterone (PR), and glucocorticoid (Fig. 5, A and B)." provenance.
- _7 value "Glucose stimulates nuclear USF2 protein accumulation through protein kinase C, p38 MAPK, and extracellular signal-regulated kinase pathways. Increased PKG activity down-regulates USF2 protein levels and its DNA binding activity under high glucose conditions, resulting in inhibition of glucose-induced TSP1 transcription and TGF-beta" provenance.
- _7 value "Glucose stimulates nuclear USF2 protein accumulation through protein kinase C, p38 MAPK, and extracellular signal-regulated kinase pathways. Increased PKG activity down-regulates USF2 protein levels and its DNA binding activity under high glucose conditions, resulting in inhibition of glucose-induced TSP1 transcription and TGF-beta" provenance.
- _6 value "Glucose stimulates nuclear USF2 protein accumulation through protein kinase C, p38 MAPK, and extracellular signal-regulated kinase pathways. Increased PKG activity down-regulates USF2 protein levels and its DNA binding activity under high glucose conditions, resulting in inhibition of glucose-induced TSP1 transcription and TGF-beta" provenance.
- _6 value "Glucose stimulates nuclear USF2 protein accumulation through protein kinase C, p38 MAPK, and extracellular signal-regulated kinase pathways. Increased PKG activity down-regulates USF2 protein levels and its DNA binding activity under high glucose conditions, resulting in inhibition of glucose-induced TSP1 transcription and TGF-beta" provenance.
- _6 value "Glucose stimulates nuclear USF2 protein accumulation through protein kinase C, p38 MAPK, and extracellular signal-regulated kinase pathways. Increased PKG activity down-regulates USF2 protein levels and its DNA binding activity under high glucose conditions, resulting in inhibition of glucose-induced TSP1 transcription and TGF-beta" provenance.
- _6 value "Glucose stimulates nuclear USF2 protein accumulation through protein kinase C, p38 MAPK, and extracellular signal-regulated kinase pathways. Increased PKG activity down-regulates USF2 protein levels and its DNA binding activity under high glucose conditions, resulting in inhibition of glucose-induced TSP1 transcription and TGF-beta" provenance.
- _9 value "Glucose stimulates nuclear USF2 protein accumulation through protein kinase C, p38 MAPK, and extracellular signal-regulated kinase pathways. Increased PKG activity down-regulates USF2 protein levels and its DNA binding activity under high glucose conditions, resulting in inhibition of glucose-induced TSP1 transcription and TGF-beta" provenance.
- _9 value "Glucose stimulates nuclear USF2 protein accumulation through protein kinase C, p38 MAPK, and extracellular signal-regulated kinase pathways. Increased PKG activity down-regulates USF2 protein levels and its DNA binding activity under high glucose conditions, resulting in inhibition of glucose-induced TSP1 transcription and TGF-beta" provenance.
- _9 value "Glucose stimulates nuclear USF2 protein accumulation through protein kinase C, p38 MAPK, and extracellular signal-regulated kinase pathways. Increased PKG activity down-regulates USF2 protein levels and its DNA binding activity under high glucose conditions, resulting in inhibition of glucose-induced TSP1 transcription and TGF-beta" provenance.
- _9 value "Glucose stimulates nuclear USF2 protein accumulation through protein kinase C, p38 MAPK, and extracellular signal-regulated kinase pathways. Increased PKG activity down-regulates USF2 protein levels and its DNA binding activity under high glucose conditions, resulting in inhibition of glucose-induced TSP1 transcription and TGF-beta" provenance.
- _4 value "Nitric oxide represses inhibitory kappaB kinase through S-nitrosylation." provenance.
- _3 value "Previously, it was shown that proinflammatory cytokines characteristic of the APR (TNF-alpha, IL-1beta, and IFNgamma) induced the expression of the PRL receptor (PRLR) by pulmonary fibroblasts in vitro." provenance.
- _3 value "Previously, it was shown that proinflammatory cytokines characteristic of the APR (TNF-alpha, IL-1beta, and IFNgamma) induced the expression of the PRL receptor (PRLR) by pulmonary fibroblasts in vitro." provenance.
- _3 value "Exogenous NmU rescued growth suppression in K562-MERT cells and stimulated the growth of primary AML cells." provenance.
- _6 value "To investigate the function of MAMLs in hematopoietic development, we introduced a dominant negative (DN) mutant of MAML1, capable of inhibiting Notch1-4, in murine hematopoietic stem cells. DNMAML1 resulted in early inhibition of T-cell development and the appearance of intrathymic B cells, phenotypes consistent with Notch1 inhibition." provenance.
- _3 value "Using the small interference RNA strategy, we demonstrated that a 70-75% reduction of 14-3-3sigma mRNA levels resulted in a similar decrease in the effects of IGF-I on cell cycle progression and proliferation in MCF-7 cells. This effect was also associated with a reduction in IGF-I-induced cyclin D1 expression. Taken together, these results suggest that 14-3-3sigma positively mediates IGF-I-induced cell cycle progression." provenance.
- _6 value "Using the small interference RNA strategy, we demonstrated that a 70-75% reduction of 14-3-3sigma mRNA levels resulted in a similar decrease in the effects of IGF-I on cell cycle progression and proliferation in MCF-7 cells. This effect was also associated with a reduction in IGF-I-induced cyclin D1 expression. Taken together, these results suggest that 14-3-3sigma positively mediates IGF-I-induced cell cycle progression." provenance.
- _4 value "T cell VPAC(2)Rs mediate changes in cytokine generation, which potently increase the Th2/Th1 ratio and consequently shift the effector responses toward allergy and inflammation." provenance.
- _3 value "Vasoactive intestinal peptide binding to VPAC(2) on CD4 T cells specifically induces an up-regulation of the Th2-type transcription factors c-Maf and JunB, which consequently enhances IL-4 and IL-5 production, leading to a Th2-type phenotype. There is strong evidence to support requirements for c-Maf, JunB, and NFAT in promoting IL-4 production. JunB, a member of the AP-1 transcription factor family, acts synergistically with c-maf to strongly activate IL-4 expression, and has also been shown to be required for IL-5 expression in Th2 cells (17, 29)." provenance.
- _3 value "To investigate the cellular fate and function of polymorphonuclear neutrophilic granulocytes (PMNs) attracted to skin wounds, we used a human skin-wounding model and microarray technology to define differentially expressed genes in PMNs from peripheral blood, and PMNs that had transmigrated to skin lesions. After migration to skin lesions, PMNs demonstrated a significant transcriptional response including genes from several different functional categories. The up-regulation of anti-apoptotic genes concomitant with the down-regulation of proapoptotic genes suggested a transient anti-apoptotic priming of PMNs. Among the up-regulated genes were cytokines and chemokines critical for chemotaxis of macrophages, T cells, and PMNs, and for the modulation of their inflammatory responses. PMNs in skin lesions down-regulated receptors mediating chemotaxis and anti-microbial activity, but up-regulated other receptors involved in inflammatory responses. These findings indicate a change of responsiveness to chemotactic and immunoregulatory mediators once PMNs have migrated to skin lesions and have been activated. Other effects of the up-regulated cytokines/chemokines/enzymes were critical for wound healing. These included the breakdown of fibrin clots and degradation of extracellular matrix, the promotion of angiogenesis, the migration and proliferation of keratinocytes and fibroblasts, the adhesion of keratinocytes to the dermal layer, and finally, the induction of anti-microbial gene expression in keratinocytes. Notably, the up-regulation of genes, which activate lysosomal proteases, indicate a priming of skin lesion-PMNs for degradation of phagocytosed material. These findings demonstrate that migration of PMNs to skin lesions induces a transcriptional activation program, which regulates cellular fate and function, and promotes wound healing." provenance.
- _3 value "To investigate the cellular fate and function of polymorphonuclear neutrophilic granulocytes (PMNs) attracted to skin wounds, we used a human skin-wounding model and microarray technology to define differentially expressed genes in PMNs from peripheral blood, and PMNs that had transmigrated to skin lesions. After migration to skin lesions, PMNs demonstrated a significant transcriptional response including genes from several different functional categories. The up-regulation of anti-apoptotic genes concomitant with the down-regulation of proapoptotic genes suggested a transient anti-apoptotic priming of PMNs. Among the up-regulated genes were cytokines and chemokines critical for chemotaxis of macrophages, T cells, and PMNs, and for the modulation of their inflammatory responses. PMNs in skin lesions down-regulated receptors mediating chemotaxis and anti-microbial activity, but up-regulated other receptors involved in inflammatory responses. These findings indicate a change of responsiveness to chemotactic and immunoregulatory mediators once PMNs have migrated to skin lesions and have been activated. Other effects of the up-regulated cytokines/chemokines/enzymes were critical for wound healing. These included the breakdown of fibrin clots and degradation of extracellular matrix, the promotion of angiogenesis, the migration and proliferation of keratinocytes and fibroblasts, the adhesion of keratinocytes to the dermal layer, and finally, the induction of anti-microbial gene expression in keratinocytes. Notably, the up-regulation of genes, which activate lysosomal proteases, indicate a priming of skin lesion-PMNs for degradation of phagocytosed material. These findings demonstrate that migration of PMNs to skin lesions induces a transcriptional activation program, which regulates cellular fate and function, and promotes wound healing." provenance.
- _3 value "To investigate the cellular fate and function of polymorphonuclear neutrophilic granulocytes (PMNs) attracted to skin wounds, we used a human skin-wounding model and microarray technology to define differentially expressed genes in PMNs from peripheral blood, and PMNs that had transmigrated to skin lesions. After migration to skin lesions, PMNs demonstrated a significant transcriptional response including genes from several different functional categories. The up-regulation of anti-apoptotic genes concomitant with the down-regulation of proapoptotic genes suggested a transient anti-apoptotic priming of PMNs. Among the up-regulated genes were cytokines and chemokines critical for chemotaxis of macrophages, T cells, and PMNs, and for the modulation of their inflammatory responses. PMNs in skin lesions down-regulated receptors mediating chemotaxis and anti-microbial activity, but up-regulated other receptors involved in inflammatory responses. These findings indicate a change of responsiveness to chemotactic and immunoregulatory mediators once PMNs have migrated to skin lesions and have been activated. Other effects of the up-regulated cytokines/chemokines/enzymes were critical for wound healing. These included the breakdown of fibrin clots and degradation of extracellular matrix, the promotion of angiogenesis, the migration and proliferation of keratinocytes and fibroblasts, the adhesion of keratinocytes to the dermal layer, and finally, the induction of anti-microbial gene expression in keratinocytes. Notably, the up-regulation of genes, which activate lysosomal proteases, indicate a priming of skin lesion-PMNs for degradation of phagocytosed material. These findings demonstrate that migration of PMNs to skin lesions induces a transcriptional activation program, which regulates cellular fate and function, and promotes wound healing." provenance.
- _3 value "To investigate the cellular fate and function of polymorphonuclear neutrophilic granulocytes (PMNs) attracted to skin wounds, we used a human skin-wounding model and microarray technology to define differentially expressed genes in PMNs from peripheral blood, and PMNs that had transmigrated to skin lesions. After migration to skin lesions, PMNs demonstrated a significant transcriptional response including genes from several different functional categories. The up-regulation of anti-apoptotic genes concomitant with the down-regulation of proapoptotic genes suggested a transient anti-apoptotic priming of PMNs. Among the up-regulated genes were cytokines and chemokines critical for chemotaxis of macrophages, T cells, and PMNs, and for the modulation of their inflammatory responses. PMNs in skin lesions down-regulated receptors mediating chemotaxis and anti-microbial activity, but up-regulated other receptors involved in inflammatory responses. These findings indicate a change of responsiveness to chemotactic and immunoregulatory mediators once PMNs have migrated to skin lesions and have been activated. Other effects of the up-regulated cytokines/chemokines/enzymes were critical for wound healing. These included the breakdown of fibrin clots and degradation of extracellular matrix, the promotion of angiogenesis, the migration and proliferation of keratinocytes and fibroblasts, the adhesion of keratinocytes to the dermal layer, and finally, the induction of anti-microbial gene expression in keratinocytes. Notably, the up-regulation of genes, which activate lysosomal proteases, indicate a priming of skin lesion-PMNs for degradation of phagocytosed material. These findings demonstrate that migration of PMNs to skin lesions induces a transcriptional activation program, which regulates cellular fate and function, and promotes wound healing." provenance.
- _3 value "To investigate the cellular fate and function of polymorphonuclear neutrophilic granulocytes (PMNs) attracted to skin wounds, we used a human skin-wounding model and microarray technology to define differentially expressed genes in PMNs from peripheral blood, and PMNs that had transmigrated to skin lesions. After migration to skin lesions, PMNs demonstrated a significant transcriptional response including genes from several different functional categories. The up-regulation of anti-apoptotic genes concomitant with the down-regulation of proapoptotic genes suggested a transient anti-apoptotic priming of PMNs. Among the up-regulated genes were cytokines and chemokines critical for chemotaxis of macrophages, T cells, and PMNs, and for the modulation of their inflammatory responses. PMNs in skin lesions down-regulated receptors mediating chemotaxis and anti-microbial activity, but up-regulated other receptors involved in inflammatory responses. These findings indicate a change of responsiveness to chemotactic and immunoregulatory mediators once PMNs have migrated to skin lesions and have been activated. Other effects of the up-regulated cytokines/chemokines/enzymes were critical for wound healing. These included the breakdown of fibrin clots and degradation of extracellular matrix, the promotion of angiogenesis, the migration and proliferation of keratinocytes and fibroblasts, the adhesion of keratinocytes to the dermal layer, and finally, the induction of anti-microbial gene expression in keratinocytes. Notably, the up-regulation of genes, which activate lysosomal proteases, indicate a priming of skin lesion-PMNs for degradation of phagocytosed material. These findings demonstrate that migration of PMNs to skin lesions induces a transcriptional activation program, which regulates cellular fate and function, and promotes wound healing." provenance.
- _3 value "To investigate the cellular fate and function of polymorphonuclear neutrophilic granulocytes (PMNs) attracted to skin wounds, we used a human skin-wounding model and microarray technology to define differentially expressed genes in PMNs from peripheral blood, and PMNs that had transmigrated to skin lesions. After migration to skin lesions, PMNs demonstrated a significant transcriptional response including genes from several different functional categories. The up-regulation of anti-apoptotic genes concomitant with the down-regulation of proapoptotic genes suggested a transient anti-apoptotic priming of PMNs. Among the up-regulated genes were cytokines and chemokines critical for chemotaxis of macrophages, T cells, and PMNs, and for the modulation of their inflammatory responses. PMNs in skin lesions down-regulated receptors mediating chemotaxis and anti-microbial activity, but up-regulated other receptors involved in inflammatory responses. These findings indicate a change of responsiveness to chemotactic and immunoregulatory mediators once PMNs have migrated to skin lesions and have been activated. Other effects of the up-regulated cytokines/chemokines/enzymes were critical for wound healing. These included the breakdown of fibrin clots and degradation of extracellular matrix, the promotion of angiogenesis, the migration and proliferation of keratinocytes and fibroblasts, the adhesion of keratinocytes to the dermal layer, and finally, the induction of anti-microbial gene expression in keratinocytes. Notably, the up-regulation of genes, which activate lysosomal proteases, indicate a priming of skin lesion-PMNs for degradation of phagocytosed material. These findings demonstrate that migration of PMNs to skin lesions induces a transcriptional activation program, which regulates cellular fate and function, and promotes wound healing." provenance.
- _3 value "To investigate the cellular fate and function of polymorphonuclear neutrophilic granulocytes (PMNs) attracted to skin wounds, we used a human skin-wounding model and microarray technology to define differentially expressed genes in PMNs from peripheral blood, and PMNs that had transmigrated to skin lesions. After migration to skin lesions, PMNs demonstrated a significant transcriptional response including genes from several different functional categories. The up-regulation of anti-apoptotic genes concomitant with the down-regulation of proapoptotic genes suggested a transient anti-apoptotic priming of PMNs. Among the up-regulated genes were cytokines and chemokines critical for chemotaxis of macrophages, T cells, and PMNs, and for the modulation of their inflammatory responses. PMNs in skin lesions down-regulated receptors mediating chemotaxis and anti-microbial activity, but up-regulated other receptors involved in inflammatory responses. These findings indicate a change of responsiveness to chemotactic and immunoregulatory mediators once PMNs have migrated to skin lesions and have been activated. Other effects of the up-regulated cytokines/chemokines/enzymes were critical for wound healing. These included the breakdown of fibrin clots and degradation of extracellular matrix, the promotion of angiogenesis, the migration and proliferation of keratinocytes and fibroblasts, the adhesion of keratinocytes to the dermal layer, and finally, the induction of anti-microbial gene expression in keratinocytes. Notably, the up-regulation of genes, which activate lysosomal proteases, indicate a priming of skin lesion-PMNs for degradation of phagocytosed material. These findings demonstrate that migration of PMNs to skin lesions induces a transcriptional activation program, which regulates cellular fate and function, and promotes wound healing." provenance.
- _3 value "To investigate the cellular fate and function of polymorphonuclear neutrophilic granulocytes (PMNs) attracted to skin wounds, we used a human skin-wounding model and microarray technology to define differentially expressed genes in PMNs from peripheral blood, and PMNs that had transmigrated to skin lesions. After migration to skin lesions, PMNs demonstrated a significant transcriptional response including genes from several different functional categories. The up-regulation of anti-apoptotic genes concomitant with the down-regulation of proapoptotic genes suggested a transient anti-apoptotic priming of PMNs. Among the up-regulated genes were cytokines and chemokines critical for chemotaxis of macrophages, T cells, and PMNs, and for the modulation of their inflammatory responses. PMNs in skin lesions down-regulated receptors mediating chemotaxis and anti-microbial activity, but up-regulated other receptors involved in inflammatory responses. These findings indicate a change of responsiveness to chemotactic and immunoregulatory mediators once PMNs have migrated to skin lesions and have been activated. Other effects of the up-regulated cytokines/chemokines/enzymes were critical for wound healing. These included the breakdown of fibrin clots and degradation of extracellular matrix, the promotion of angiogenesis, the migration and proliferation of keratinocytes and fibroblasts, the adhesion of keratinocytes to the dermal layer, and finally, the induction of anti-microbial gene expression in keratinocytes. Notably, the up-regulation of genes, which activate lysosomal proteases, indicate a priming of skin lesion-PMNs for degradation of phagocytosed material. These findings demonstrate that migration of PMNs to skin lesions induces a transcriptional activation program, which regulates cellular fate and function, and promotes wound healing." provenance.
- _3 value "To investigate the cellular fate and function of polymorphonuclear neutrophilic granulocytes (PMNs) attracted to skin wounds, we used a human skin-wounding model and microarray technology to define differentially expressed genes in PMNs from peripheral blood, and PMNs that had transmigrated to skin lesions. After migration to skin lesions, PMNs demonstrated a significant transcriptional response including genes from several different functional categories. The up-regulation of anti-apoptotic genes concomitant with the down-regulation of proapoptotic genes suggested a transient anti-apoptotic priming of PMNs. Among the up-regulated genes were cytokines and chemokines critical for chemotaxis of macrophages, T cells, and PMNs, and for the modulation of their inflammatory responses. PMNs in skin lesions down-regulated receptors mediating chemotaxis and anti-microbial activity, but up-regulated other receptors involved in inflammatory responses. These findings indicate a change of responsiveness to chemotactic and immunoregulatory mediators once PMNs have migrated to skin lesions and have been activated. Other effects of the up-regulated cytokines/chemokines/enzymes were critical for wound healing. These included the breakdown of fibrin clots and degradation of extracellular matrix, the promotion of angiogenesis, the migration and proliferation of keratinocytes and fibroblasts, the adhesion of keratinocytes to the dermal layer, and finally, the induction of anti-microbial gene expression in keratinocytes. Notably, the up-regulation of genes, which activate lysosomal proteases, indicate a priming of skin lesion-PMNs for degradation of phagocytosed material. These findings demonstrate that migration of PMNs to skin lesions induces a transcriptional activation program, which regulates cellular fate and function, and promotes wound healing." provenance.
- _3 value "To investigate the cellular fate and function of polymorphonuclear neutrophilic granulocytes (PMNs) attracted to skin wounds, we used a human skin-wounding model and microarray technology to define differentially expressed genes in PMNs from peripheral blood, and PMNs that had transmigrated to skin lesions. After migration to skin lesions, PMNs demonstrated a significant transcriptional response including genes from several different functional categories. The up-regulation of anti-apoptotic genes concomitant with the down-regulation of proapoptotic genes suggested a transient anti-apoptotic priming of PMNs. Among the up-regulated genes were cytokines and chemokines critical for chemotaxis of macrophages, T cells, and PMNs, and for the modulation of their inflammatory responses. PMNs in skin lesions down-regulated receptors mediating chemotaxis and anti-microbial activity, but up-regulated other receptors involved in inflammatory responses. These findings indicate a change of responsiveness to chemotactic and immunoregulatory mediators once PMNs have migrated to skin lesions and have been activated. Other effects of the up-regulated cytokines/chemokines/enzymes were critical for wound healing. These included the breakdown of fibrin clots and degradation of extracellular matrix, the promotion of angiogenesis, the migration and proliferation of keratinocytes and fibroblasts, the adhesion of keratinocytes to the dermal layer, and finally, the induction of anti-microbial gene expression in keratinocytes. Notably, the up-regulation of genes, which activate lysosomal proteases, indicate a priming of skin lesion-PMNs for degradation of phagocytosed material. These findings demonstrate that migration of PMNs to skin lesions induces a transcriptional activation program, which regulates cellular fate and function, and promotes wound healing." provenance.
- _3 value "To investigate the cellular fate and function of polymorphonuclear neutrophilic granulocytes (PMNs) attracted to skin wounds, we used a human skin-wounding model and microarray technology to define differentially expressed genes in PMNs from peripheral blood, and PMNs that had transmigrated to skin lesions. After migration to skin lesions, PMNs demonstrated a significant transcriptional response including genes from several different functional categories. The up-regulation of anti-apoptotic genes concomitant with the down-regulation of proapoptotic genes suggested a transient anti-apoptotic priming of PMNs. Among the up-regulated genes were cytokines and chemokines critical for chemotaxis of macrophages, T cells, and PMNs, and for the modulation of their inflammatory responses. PMNs in skin lesions down-regulated receptors mediating chemotaxis and anti-microbial activity, but up-regulated other receptors involved in inflammatory responses. These findings indicate a change of responsiveness to chemotactic and immunoregulatory mediators once PMNs have migrated to skin lesions and have been activated. Other effects of the up-regulated cytokines/chemokines/enzymes were critical for wound healing. These included the breakdown of fibrin clots and degradation of extracellular matrix, the promotion of angiogenesis, the migration and proliferation of keratinocytes and fibroblasts, the adhesion of keratinocytes to the dermal layer, and finally, the induction of anti-microbial gene expression in keratinocytes. Notably, the up-regulation of genes, which activate lysosomal proteases, indicate a priming of skin lesion-PMNs for degradation of phagocytosed material. These findings demonstrate that migration of PMNs to skin lesions induces a transcriptional activation program, which regulates cellular fate and function, and promotes wound healing." provenance.
- _3 value "To investigate the cellular fate and function of polymorphonuclear neutrophilic granulocytes (PMNs) attracted to skin wounds, we used a human skin-wounding model and microarray technology to define differentially expressed genes in PMNs from peripheral blood, and PMNs that had transmigrated to skin lesions. After migration to skin lesions, PMNs demonstrated a significant transcriptional response including genes from several different functional categories. The up-regulation of anti-apoptotic genes concomitant with the down-regulation of proapoptotic genes suggested a transient anti-apoptotic priming of PMNs. Among the up-regulated genes were cytokines and chemokines critical for chemotaxis of macrophages, T cells, and PMNs, and for the modulation of their inflammatory responses. PMNs in skin lesions down-regulated receptors mediating chemotaxis and anti-microbial activity, but up-regulated other receptors involved in inflammatory responses. These findings indicate a change of responsiveness to chemotactic and immunoregulatory mediators once PMNs have migrated to skin lesions and have been activated. Other effects of the up-regulated cytokines/chemokines/enzymes were critical for wound healing. These included the breakdown of fibrin clots and degradation of extracellular matrix, the promotion of angiogenesis, the migration and proliferation of keratinocytes and fibroblasts, the adhesion of keratinocytes to the dermal layer, and finally, the induction of anti-microbial gene expression in keratinocytes. Notably, the up-regulation of genes, which activate lysosomal proteases, indicate a priming of skin lesion-PMNs for degradation of phagocytosed material. These findings demonstrate that migration of PMNs to skin lesions induces a transcriptional activation program, which regulates cellular fate and function, and promotes wound healing." provenance.
- _3 value "To investigate the cellular fate and function of polymorphonuclear neutrophilic granulocytes (PMNs) attracted to skin wounds, we used a human skin-wounding model and microarray technology to define differentially expressed genes in PMNs from peripheral blood, and PMNs that had transmigrated to skin lesions. After migration to skin lesions, PMNs demonstrated a significant transcriptional response including genes from several different functional categories. The up-regulation of anti-apoptotic genes concomitant with the down-regulation of proapoptotic genes suggested a transient anti-apoptotic priming of PMNs. Among the up-regulated genes were cytokines and chemokines critical for chemotaxis of macrophages, T cells, and PMNs, and for the modulation of their inflammatory responses. PMNs in skin lesions down-regulated receptors mediating chemotaxis and anti-microbial activity, but up-regulated other receptors involved in inflammatory responses. These findings indicate a change of responsiveness to chemotactic and immunoregulatory mediators once PMNs have migrated to skin lesions and have been activated. Other effects of the up-regulated cytokines/chemokines/enzymes were critical for wound healing. These included the breakdown of fibrin clots and degradation of extracellular matrix, the promotion of angiogenesis, the migration and proliferation of keratinocytes and fibroblasts, the adhesion of keratinocytes to the dermal layer, and finally, the induction of anti-microbial gene expression in keratinocytes. Notably, the up-regulation of genes, which activate lysosomal proteases, indicate a priming of skin lesion-PMNs for degradation of phagocytosed material. These findings demonstrate that migration of PMNs to skin lesions induces a transcriptional activation program, which regulates cellular fate and function, and promotes wound healing." provenance.
- _5 value "E(2) inhibited resveratrol-induced, p53-directed transcriptional activity." provenance.
- _2 value "Resveratrol, a naturally occurring stilbene, induced apoptosis in human breast cancer MCF-7 cells." provenance.
- _2 value "Resveratrol, a naturally occurring stilbene, induced apoptosis in human breast cancer MCF-7 cells." provenance.
- _5 value "These effects of E(2) on resveratrol action were blocked by ICI 182,780 (ICI), an inhibitor of the nuclear oestrogen receptor-alpha (ER)" provenance.
- _3 value "this effect was dependent on mitogen-activated protein kinase (MAPK, ERK1/2) activation and was associated with serine phosphorylation and acetylation of p53" provenance.
- _3 value "Activin A stimulated vascular endothelial growth factor gene transcription through Sp1-dependent induction of vascular endothelial growth factor promoter activity." provenance.
- _3 value "After interferon-alpha treatment, the expression of four genes (vascular endothelial growth factor, tyrosine phosphate 1E, serine protein with IGF-binding motif and one gene of clathrin light chain) in HepG(2)2.2.15 were up-regulated, while one gene encoding a GTP-binding protein, two genes of interferon-induced kinases and two proto-oncogenes were further down- regulated." provenance.
- _7 value "Dok-1 is a common substrate of many protein tyrosine kinases (PTKs). It recruits rasGAP and other SH2-containing proteins and negatively regulates Ras-Erk signalling downstream of PTKs" provenance.
- _3 value "Although E2F1 was stabilized by ultraviolet (UV) irradiation, the mRNA expression level of TopBP1 was suppressed" provenance.
- _5 value "As shown in Fig. 3A, activins AB and B augmented (SBE)4-lux reporter activity in MIN6 cells. To verify that activin isoforms signal is mediated via ALK7 in MIN6 cells, we measured the activity of the dominant negative ALK7 construct (D/N ALK7 cDNA). D/N ALK7 cDNA lacks the intracellular kinase domain but retains the extracellular and transmembrane domains. The specificity of D/N ALK7 was confirmed in HEK293 cells (Fig. 3B). The activity of ALK4-dependent activin signaling was barely affected in the D/N ALK7 construct, but the ALK7-augmented response to activins B and AB was significantly inhibited. Thus, D/N ALK7 is a dominant negative inhibitor of ALK7 signaling but not of the ALK4 pathway ( Fig. 3B). As shown in Fig. 3C, D/N ALK7 completely blocked the responses of MIN6 cells to activins AB and B, confirming that activin isoforms signal via ALK7 in MIN6 cells" provenance.
- _5 value "As shown in Fig. 3A, activins AB and B augmented (SBE)4-lux reporter activity in MIN6 cells. To verify that activin isoforms signal is mediated via ALK7 in MIN6 cells, we measured the activity of the dominant negative ALK7 construct (D/N ALK7 cDNA). D/N ALK7 cDNA lacks the intracellular kinase domain but retains the extracellular and transmembrane domains. The specificity of D/N ALK7 was confirmed in HEK293 cells (Fig. 3B). The activity of ALK4-dependent activin signaling was barely affected in the D/N ALK7 construct, but the ALK7-augmented response to activins B and AB was significantly inhibited. Thus, D/N ALK7 is a dominant negative inhibitor of ALK7 signaling but not of the ALK4 pathway ( Fig. 3B). As shown in Fig. 3C, D/N ALK7 completely blocked the responses of MIN6 cells to activins AB and B, confirming that activin isoforms signal via ALK7 in MIN6 cells" provenance.
- _6 value "Furthermore, GH induced rapid, time- and dose-dependent signaling events in LNCaP cells, including phosphorylation of JAK2 tyrosine kinase, of GHR itself and of STAT5A (JAK2-STAT5A pathway), of p42/p44 MAPK and of Akt/PKB." provenance.
- _3 value "Additionally, treatment with tumor necrosis factor-alpha and exposure to UV radiation induced the transcriptional activation of Ipaf in human leukemia HL-60 cells." provenance.
- _6 value "These cells also responded with an enhanced release of PGE(2) and COX-2 protein expression following addition of the soluble stimulants, LPS and heat-activated IgG." provenance.
- _3 value "These cells also responded with an enhanced release of PGE(2) and COX-2 protein expression following addition of the soluble stimulants, LPS and heat-activated IgG." provenance.
- _4 value "The protective effect of PDTC suggests that L-homocysteine inactivates DDAH in neurons by reacting with the cysteine residue in its active site." provenance.
- _3 value "ATF3 is induced in beta cells by signals relevant to beta-cell destruction: proinflammatory cytokines, nitric oxide, and high concentrations of glucose and palmitate." provenance.
- _3 value "ATF3 is induced in beta cells by signals relevant to beta-cell destruction: proinflammatory cytokines, nitric oxide, and high concentrations of glucose and palmitate." provenance.
- _2 value "ATF3 is induced in beta cells by signals relevant to beta-cell destruction: proinflammatory cytokines, nitric oxide, and high concentrations of glucose and palmitate." provenance.
- _3 value "ATF3 is induced in beta cells by signals relevant to beta-cell destruction: proinflammatory cytokines, nitric oxide, and high concentrations of glucose and palmitate." provenance.
- _4 value "An important finding is that intact BRCA1 also prevents EGF and IGF-I signaling through ERK to cell proliferation. EGF and IGF-1 are strongly implicated in the biology of human breast cancer, where they signal through this member of the MAP kinase family to cell growth (27, 52)." provenance.
- _4 value "We examined the impact of BRCA1 on membrane estrogen and growth factor receptor signaling to breast cancer cell proliferation. MCF-7 and ZR-75-1 cells showed a rapid and sustained activation of extracellular signal-related kinase (ERK) in response to estradiol (E2) that was substantially prevented by wild-type (wt) but not mutant BRCA1." provenance.
- _6 value "CD40 lacks intrinsic catalytic activity, but the cytoplasmic domain of CD40 has two binding sites for TRAF...TRAFs 1, 2, 3, 5, and 6 have been found in association with CD40, and these adaptors couple CD40 to the phosphoinositide 3-kinase (PI3K), phospholipase C�?³ (PLC-�?³), mitogen-activated protein kinase (MAPK-ERK, p38, and JNK), and nuclear factor �?ºB (NF-�?ºB) signaling pathways" provenance.
- _6 value "CD40 lacks intrinsic catalytic activity, but the cytoplasmic domain of CD40 has two binding sites for TRAF...TRAFs 1, 2, 3, 5, and 6 have been found in association with CD40, and these adaptors couple CD40 to the phosphoinositide 3-kinase (PI3K), phospholipase C�?³ (PLC-�?³), mitogen-activated protein kinase (MAPK-ERK, p38, and JNK), and nuclear factor �?ºB (NF-�?ºB) signaling pathways" provenance.
- _6 value "CD40 signaling also acts to suppress the expression of the gene encoding CTCF, which is a transcription factor that represses c-myc expression, thus allowing sustained c-myc expression and cell cycle progression" provenance.
- _5 value "CD40 signaling also acts to suppress the expression of the gene encoding CTCF, which is a transcription factor that represses c-myc expression, thus allowing sustained c-myc expression and cell cycle progression" provenance.
- _5 value "CTCF induces expression of the gene encoding p19Arf, which sequesters the p53 inhibitor MDM2, resulting in activation of p53" provenance.
- _4 value "In fact, soluble KIT ligand is sufficient to induce tyrosinase expression in Ednrb-deficient cultures." provenance.
- _3 value "One of the possible inducers of VEGF in tumor cells is nitric oxide (NO), which is synthesized by NO synthase and stimulates soluble guanylate cyclase (GC) in tumor cells" provenance.
- _4 value "Furthermore, PKI166 blocked tyrosine phosphorylation of Dsg2 and plakoglobin following epidermal growth factor stimulation," provenance.
- _5 value "Furthermore, PKI166 blocked tyrosine phosphorylation of Dsg2 and plakoglobin following epidermal growth factor stimulation," provenance.
- _3 value "QUIN induces astrocytes to produce large quantities of MCP-1 (CCL2), and lesser amounts of RANTES (CCL5), IL-8 (CXCL8). QUIN also increases SDF-1alpha (CXCL12), HuMIG (CXCL9) and fractalkine (CX3CL1) mRNA expression. Moreover, QUIN leads to up-regulation of the chemokine receptor expression of CXCR4, CCR5, and CCR3" provenance.
- _3 value "QUIN induces astrocytes to produce large quantities of MCP-1 (CCL2), and lesser amounts of RANTES (CCL5), IL-8 (CXCL8). QUIN also increases SDF-1alpha (CXCL12), HuMIG (CXCL9) and fractalkine (CX3CL1) mRNA expression. Moreover, QUIN leads to up-regulation of the chemokine receptor expression of CXCR4, CCR5, and CCR3" provenance.
- _3 value "QUIN induces astrocytes to produce large quantities of MCP-1 (CCL2), and lesser amounts of RANTES (CCL5), IL-8 (CXCL8). QUIN also increases SDF-1alpha (CXCL12), HuMIG (CXCL9) and fractalkine (CX3CL1) mRNA expression. Moreover, QUIN leads to up-regulation of the chemokine receptor expression of CXCR4, CCR5, and CCR3" provenance.
- _3 value "QUIN induces astrocytes to produce large quantities of MCP-1 (CCL2), and lesser amounts of RANTES (CCL5), IL-8 (CXCL8). QUIN also increases SDF-1alpha (CXCL12), HuMIG (CXCL9) and fractalkine (CX3CL1) mRNA expression. Moreover, QUIN leads to up-regulation of the chemokine receptor expression of CXCR4, CCR5, and CCR3" provenance.
- _6 value "The conclusion that VEGF treatment leads to a Rap1/Bmx complex was confirmed by an experiment in which cell lysates from VEGF and control cells were immunoprecipitated with Bmx antibodies and Western blotting was done using anti-Rap1 antibodies. VEGF treatment led to the recruitment of Bmx to the CAS scaffolding protein, and inhibition of the Bmx kinase blocked VEGF-induced cell migration." provenance.
- _6 value "BDNF caused a rapid and time-dependent decrease of nuclear FOXO3a with a corresponding increase of cytosolic FOXO3a." provenance.
- _6 value "Smads 3 and 4 have specifically been shown to take part in TGF-beta-mediated CTCF/Smads complex binding of the APP gene promoter that up-regulates APP expression In addition, TGF-beta has been shown to stimulate Smads interaction with the stimulating protein 1 (SP1) transcription factor" provenance.
- _7 value "Smads 3 and 4 have specifically been shown to take part in TGF-beta-mediated CTCF/Smads complex binding of the APP gene promoter that up-regulates APP expression In addition, TGF-beta has been shown to stimulate Smads interaction with the stimulating protein 1 (SP1) transcription factor" provenance.
- _3 value "loss of IFN-inducible IFI 16 expression in human fibroblasts allows bypass of cellular senescence." provenance.
- _3 value "For example, in an expression profile analysis comparing melanoma cells and their highly metastatic derivatives, RhoC was identified as essential for pulmonary metastasis by melanoma cells that were injected intravenously into mice (Clark et al., 2000). Recently, a set of genes, including osteopontin and IL-11, were shown to promote bone metastasis when human breast cancer cells were injected via the intracardiac route (Kang et al., 2003)." provenance.
- _7 value "Overexpression of Rb inhibited ASK1-induced apoptosis; in addition, an ASK1 mutant incapable of binding Rb could not induce apoptosis, indicating that ASK1 has to overcome the antiapoptotic properties of Rb to kill cells." provenance.