Matches in Nanopublications for { ?s <http://www.w3.org/ns/prov#value> ?o ?g. }
- _4 value "Treatment of primary human monocytes with TGF-beta inhibited basal as well as dexamethasone-induced CD163 mRNA and protein expression." provenance.
- _6 value "The extent of the acetylation is up-regulated by the transforming growth factor-beta signaling pathway and down-regulated by histone deacetylase activities." provenance.
- _5 value "Orlistat reduced phosphorylation of the Rb protein, up-regulated p27Kip1, and down-regulated Skp2. These effects were evident at levels of the drug consistent with the cellular IC50 of Orlistat for inhibition of the FAS thioesterase (1-3 M). To independently verify that the effects of Orlistat could be attributed to its ability to block FAS, similar experiments were conducted with siRNA-targeting FAS (Fig. 4B). Like Orlistat, the siRNA-targeting FAS decreased the phosphorylation of Rb, increased the level of p27Kip1, and reduced the level of Skp2. An siRNA-targeting Skp2 had identical effects upon its downstream target, p27Kip1, and upon the phosphorylation status of the Rb protein. Together, these findings provide strong support for the idea that a FAS blockade acts upon the Rb pathway via regulation of Skp2 and also indicate that a FAS blockade is likely to have effects similar to an Skp2 blockade." provenance.
- _4 value "Orlistat, a drug approved for treating obesity, is used as a potent inhibitor of the thioesterase function of FAS." provenance.
- _4 value "Furthermore, TWEAK induced rapid phosphorylation of IkappaB-alpha in human keratinocytes." provenance.
- _3 value "for both p16(INK4a) and p14(ARF), promoter methylation is the commonest mechanism of gene inactivation." provenance.
- _4 value "MCF-7 cells stably expressing PLCdelta4 demonstrates several phenotypes of transformation, such as rapid proliferation in low serum, formation of colonies in soft agar, and capacity to form densely packed spheroids in low-attachment plates." provenance.
- _6 value "Overexpression of PLCdelta4 selectively activates protein kinase C-phi and upregulates the expression of epidermal growth factor receptors EGFR/erbB1 and HER2/erbB2, leading to constitutive activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathway in MCF-7 cells. " provenance.
- _6 value "title := \"Transcriptional regulation by the repressor of estrogen receptor activity via recruitment of histone deacetylases.\" Using the yeast two-hybrid system, we isolated the repressor of estrogen receptor activity (REA) as a novel HDAC1-associated protein. We demonstrated the in vivo interaction of REA with HDAC1 and characterized the respective domains required for their interaction in vitro. In addition, we found that REA also associates with the class II histone deacetylase HDAC5. In luciferase reporter assays, REA decreased transcription, and this repression was sensitive to the deacetylase inhibitor trichostatin A." provenance.
- _5 value "AKAP121 binds to and redistributes PTPD1 from the cytoplasm to mitochondria and inhibits EGF signaling." provenance.
- _6 value "PTPD1 activates src tyrosine kinase and increases the magnitude and duration of epidermal growth factor (EGF) signaling. EGF receptor phosphorylation and downstream activation of ERK 1/2 and Elk1-dependent gene transcription are enhanced by PTPD1." provenance.
- _6 value "EGF induced rapid and sustained GTP loading of Rap2B, binding of Rap2B to PLC-epsilon, and Rap2B-dependent translocation of PLC-epsilon to the plasma membrane." provenance.
- _4 value "Hepatic gluconeogenesis is essential for maintenance of normal blood glucose concentrations and is regulated by opposing stimulatory (cyclic adenosine monophosphate, cAMP) and inhibitory (insulin) signaling pathways. The cAMP signaling pathway leads to phosphorylation of cAMP response element-binding (CREB) protein, resulting in recruitment of the coactivators CREB-binding protein (CBP) and p300 and subsequent activation of gluconeogenesis." provenance.
- _5 value "Table 1. Genes markedly perturbed by HNF-1b RNAi" provenance.
- _5 value "Table 1. Genes markedly perturbed by HNF-1b RNAi" provenance.
- _5 value "Table 1. Genes markedly perturbed by HNF-1b RNAi" provenance.
- _5 value "Table 1. Genes markedly perturbed by HNF-1b RNAi" provenance.
- _5 value "Table 1. Genes markedly perturbed by HNF-1b RNAi" provenance.
- _5 value "Table 1. Genes markedly perturbed by HNF-1b RNAi" provenance.
- _6 value "Since genes encoding ecto-5'-nucleotidase (eN) and adenosine deaminase (ADA) contain TCF/LEF consensus binding sites, we asked whether Wnt/beta-catenin signaling, a pathway that is deregulated in several human tumors, targets the expression of these genes and thus influence extracellular adenosine generation. Our results show that beta-catenin strongly increased the activity of the 969-bp promoter of eN and this increase depended on the presence of TCF-1 transcription factor." provenance.
- _3 value "See Table 6: Microarray and reverse transcription PCR (RT-PCR) comparison. All genes have increased expression in response to Zebularine greater than or equal to 1.5 compared to control." provenance.
- _3 value "See Table 6: Microarray and reverse transcription PCR (RT-PCR) comparison. All genes have increased expression in response to Zebularine greater than or equal to 1.5 compared to control." provenance.
- _4 value "SIRT1 physically interacts with the RelA/p65 subunit of NF-kappaB and inhibits transcription by deacetylating RelA/p65 at lysine 310." provenance.
- _4 value "Ovalbumin (OVA) inhalation in sensitized mice induced substantial cytokine release into Bronchoalveolar lavage fluid (BALF) as compared with untreated cells. MEK1/2 inhibitor, U0126 significantly reduced IL5 levels in BAL fluid in a dose-dependent manner. These results suggest that OVA-induced up-regulation of IL5 production was mediated through MEK/ERK pathway." provenance.
- _5 value "Such action of HGF was dependent on the activation of extracellular signal-regulated kinase-1 and -2" provenance.
- _3 value "These results indicate that PEBP not only inhibits cell proliferation but also induces differentiation of human keratinocytes." provenance.
- _4 value "MTP18 mRNA as well as protein expression is dependent on PI 3-kinase activity" provenance.
- _4 value "TABLE I Sema 3A regulates gene expression in PC12 cells and hippocampal neurons (PC12+SEMA3A and PC12+NGF columns)" provenance.
- _3 value "Table II. The MCF-7a genomic response to H2O2 at 5 hours. Genes with a significant change in gene expression between treated and untreated samples in 2 independent experiments are listed." provenance.
- _3 value "Table II. The MCF-7a genomic response to H2O2 at 5 hours. Genes with a significant change in gene expression between treated and untreated samples in 2 independent experiments are listed." provenance.
- _3 value "Table II. The MCF-7a genomic response to H2O2 at 5 hours. Genes with a significant change in gene expression between treated and untreated samples in 2 independent experiments are listed." provenance.
- _3 value "Table II. The MCF-7a genomic response to H2O2 at 5 hours. Genes with a significant change in gene expression between treated and untreated samples in 2 independent experiments are listed." provenance.
- _3 value "Table II. The MCF-7a genomic response to H2O2 at 5 hours. Genes with a significant change in gene expression between treated and untreated samples in 2 independent experiments are listed." provenance.
- _3 value "Table II. The MCF-7a genomic response to H2O2 at 5 hours. Genes with a significant change in gene expression between treated and untreated samples in 2 independent experiments are listed." provenance.
- _3 value "Table II. The MCF-7a genomic response to H2O2 at 5 hours. Genes with a significant change in gene expression between treated and untreated samples in 2 independent experiments are listed." provenance.
- _3 value "Table III. The MCF-7b genomic response to H2O2 at 5 hours. Genes with a significant change in gene expression between treated and untreated samples in 2 independent experiments are listed." provenance.
- _3 value "Table III. The MCF-7b genomic response to H2O2 at 5 hours. Genes with a significant change in gene expression between treated and untreated samples in 2 independent experiments are listed." provenance.
- _3 value "Table IV. The MRC-9 genomic response to H2O2 at 5 hours. Genes with a significant change in gene expression between treated and untreated samples in 2 independent experiments are listed." provenance.
- _3 value "Table IV. The MRC-9 genomic response to H2O2 at 5 hours. Genes with a significant change in gene expression between treated and untreated samples in 2 independent experiments are listed." provenance.
- _3 value "Table IV. The MRC-9 genomic response to H2O2 at 5 hours. Genes with a significant change in gene expression between treated and untreated samples in 2 independent experiments are listed." provenance.
- _3 value "Table IV. The MRC-9 genomic response to H2O2 at 5 hours. Genes with a significant change in gene expression between treated and untreated samples in 2 independent experiments are listed." provenance.
- _3 value "Table IV. The MRC-9 genomic response to H2O2 at 5 hours. Genes with a significant change in gene expression between treated and untreated samples in 2 independent experiments are listed." provenance.
- _3 value "Table IV. The MRC-9 genomic response to H2O2 at 5 hours. Genes with a significant change in gene expression between treated and untreated samples in 2 independent experiments are listed." provenance.
- _3 value "Table IV. The MRC-9 genomic response to H2O2 at 5 hours. Genes with a significant change in gene expression between treated and untreated samples in 2 independent experiments are listed." provenance.
- _6 value "Modified assertion" provenance.
- _5 value "Lastly, PV1 upregulation by PMA required the activation of Erk1/2 MAP kinase pathway and was protein kinase C independent" provenance.
- _3 value "Using microarray analysis of VHL mutated and re-introduced cells, we found that one of the prolyl hydroxylases (PHD3) is coordinately expressed with known HIF target genes, while the other two family members (PHD1 and 2) did not respond to VHL." provenance.
- _8 value "Tbx3 is able to repress Nppa and Cx40 promoter activity and abolish the synergistic activation of the Nppa promoter by Tbx5 and Nkx2.5." provenance.
- _3 value "Jubilant sentence: AR (amphiregulin) was significantly up-regulated in cells treated with natural estrogens like 17 beta-estradiol, estriol, estrone and phytoestrogen genistein. AR was increased almost 5-folds in cells treated with estrogen compared to control cells." provenance.
- _4 value "Cells stimulated with epidermal growth factor, Akt, were activated through phosphorylation at Ser-473 and Thr-308. EGF was found to be a weak activator of Akt." provenance.
- _3 value "NDRG2 gene can arrest HepG2 cell proliferation and induce their apoptosis." provenance.
- _3 value "NDRG2 gene can arrest HepG2 cell proliferation and induce their apoptosis." provenance.
- _4 value "Pretreatment of HT29 cells with increasing concentrations of PD98059 (a specific inhibitor of ERK 1/2) resulted in a dose-dependent decrease in the cell number induced by thrombin (10 nM/L), suggesting that cell proliferation induced by thrombin or AP1 involves the phosphorylation of ERKs in these cells." provenance.
- _3 value "Our data suggest that up-regulation of SOCS2 in neuronal progenitor cells derived from the adult SVZ may regulate EPO enhanced neuronal differentiation" provenance.
- _5 value "from full text:Our data showed that phosphorylation of Pak1 Ser-199/204 was enhanced by DSCAM (Fig. 5B), whereas Pak1 phosphorylation induced by RacL61 was observed as a positive control." provenance.
- _3 value "the upregulation of nNOS was associated with a decreased level of production of bioactive NO and by an increase in the level of generation of reactive oxygen species (ROS)" provenance.
- _4 value "higher expression level of CP and FP was also confirmed by Western blotting" provenance.
- _4 value "In Raldh2(-/-) embryos,there was down-regulation of TGF-beta1, fibronectin (Fn) and integrin alpha5,which was associated with decreased visceral endoderm survival and production of VEGFA, Indian hedgehog (IHH), and bFGF." provenance.
- _5 value "Bach1 is a transcriptional repressor of heme oxygenase-1 and beta-globin genes, both of which are known to be transcriptionally induced by heme." provenance.
- _3 value "As expected, monocytes from CCR2/ mice have an abnormality in their migratory ability." provenance.
- _3 value "Overexpression of RIP5 also induces DNA fragmentation and this is blocked by the caspase inhibitor crmA." provenance.
- _3 value "Here we show that ATM kinase activity is inhibited by poly(ADP-ribose) polymerase-1 (PARP-1) in vitro. It was shown by biochemical fractionation procedure that PARP-1 as well as ATM increases at chromatin level after induction of DSB with neocarzinostatin (NCS)." provenance.
- _6 value "IGFBP-3 inhibits the binding of IGF-I to its receptor and thereby inhibits IGF-I-stimulated growth." provenance.
- _7 value "IGFBP-3 stimulated TGF-betaRII-dependent serine phosphorylation (activation) of both TGF-betaRI and of its primary substrate, Smad2(Ser465/467)." provenance.
- _5 value "IGFBP-3 stimulated TGF-betaRII-dependent serine phosphorylation (activation) of both TGF-betaRI and of its primary substrate, Smad2(Ser465/467)." provenance.
- _5 value "IGFBP-3 stimulated TGF-betaRII-dependent serine phosphorylation (activation) of both TGF-betaRI and of its primary substrate, Smad2(Ser465/467)." provenance.
- _5 value "IGFBP-3 stimulated TGF-betaRII-dependent serine phosphorylation (activation) of both TGF-betaRI and of its primary substrate, Smad2(Ser465/467)." provenance.
- _7 value "effects of IGFBP-3 on Smad2 phosphorylation and on smooth muscle cell proliferation were independent of TGF-beta1 and were abolished by transfection of Smad2 siRNA." provenance.
- _3 value "SPARC fragment" provenance.
- _4 value "VEGF gene expression is upregulated by a host of stimuli, including estrogen, nitric oxide and a variety of growth factors, such as fibroblast growth factor-4, PDGF, TNF-alpha, EGF, TGFbeta, keratinocyte growth factor, IL6, IL1B, and IGF1" provenance.
- _7 value "VEGF-B and PIGF binding and activating only VEGFR1" provenance.
- _7 value "VEGF-C and VEGF-D bind a 3rd receptor, VEGFR3 (FLT4), through which they mediate lymphangiogenesis and also show some activity toward VEGFR2" provenance.
- _2 value "hypoxia, hypoglycemia and mechanical stress can serve as stimuli" 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.
- _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 "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.
- _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.
- _4 value "Table 2. Targets and their Inhibitors Target Drug Form Stage References EGFR IMC-225 ZD-1839 EGFR-AS monoclonal antibodies kinase inhibitor antisense oligonucleotide Phase II and III Phase I and II preclinical Ciardiello and Tortora 2001 (91) Johnston et al. 2003 (94) Li et al. 2002 (95)" provenance.
- _5 value "The upregulation of MAPK activity was detected in breast cancers [77], and ERK1/2, JNK and p38 were identified in the stimulation of uPA and uPAR expression [78, 79]. Furthermore, inhibition of ERK1/2 and p38 down-regulated the expression of uPA/uPAR, which resulted in the inhibition of migration and decreased cell proliferation of the highly invasive breast cancer cells MDA-MB-231 [" provenance.
- _3 value "Knockdown of SRF protein levels in human and rat endothelial cells abolished VEGF-induced in vitro angiogenesis, impaired endothelial cell migration and proliferation, and inhibited VEGF-induced actin polymerization and immediate early gene expression." provenance.
- _3 value "Knockdown of SRF protein levels in human and rat endothelial cells abolished VEGF-induced in vitro angiogenesis, impaired endothelial cell migration and proliferation, and inhibited VEGF-induced actin polymerization and immediate early gene expression." provenance.
- _4 value "Insulin-degrading enzyme (IDE) is a protease that degrades insulin and the beta-amyloid (Abeta) peptide implicated in Alzheimer's disease (AD)." provenance.
- _5 value "Depletion of cholesterol from the cells using beta-cyclodextrin blocked insulin stimulation of glucose uptake, insulin inhibition of perilipin phosphorylation in response to isoproterenol, and insulin stimulation of protein kinase B and Map-kinases extracellular signal-related kinase (ERK)1/2 phosphorylation" provenance.
- _3 value "Depletion of cholesterol from the cells using beta-cyclodextrin blocked insulin stimulation of glucose uptake, insulin inhibition of perilipin phosphorylation in response to isoproterenol, and insulin stimulation of protein kinase B and Map-kinases extracellular signal-related kinase (ERK)1/2 phosphorylation" 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.
- _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.
- _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.
- _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.
- _5 value "Significantly, only AML cells expressed the cognate receptor of NmU, NMU1R, suggesting the presence of a novel autocrine loop." provenance.
- _4 value "Preincubation with the phosphoinositide 3'-kinase inhibitor LY294002 significantly reduced the effects of IGF-I on 14-3-3sigma gene expression in these cells, suggesting that this effect of IGF-I occurs via the phosphoinositide 3'-kinase pathway." 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.