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- _4 value "In human circulating monocytes, inhibition of PDE4 by rolipram markedly suppresses TNF- synthesis and release in response to LPS; ... LPS stimulation of macrophages induces a large increase in TNF- mRNA by increasing gene transcription via activation of the transcriptional factors NF-B (13-15), c-jun, and c-fos (16). ... A study investigating the control of TNF- synthesis by using reporter constructs has demonstrated that this AU-rich element and the flanking sequences are sufficient to mediate a more than 200-fold increase in the LPS-dependent synthesis of the reporter protein. This element is involved in both the control of mRNA degradation and its translation This increase is not due to a change in cytoplasmic mRNA concentration but rather to a reversal of the translation repression in response to LPS ...The consequent increase in PDE activity leads to a decrease in cAMP, thus removing the cAMP constraint and allowing a full induction of TNF- mRNA and protein synthesis. The induction of PDE4B should then be viewed as a positive feedback loop that contributes to a full activation of the cytokine responses." provenance.
- _4 wasQuotedFrom 12032334 provenance.