4.5 Article

Integration of the NF-κB and mitogen-activated protein kinase/AP-1 pathways at the collagenase-1 promoter:: Divergence of IL-1 and TNF-dependent signal transduction in rabbit primary synovial fibroblasts

期刊

CYTOKINE
卷 12, 期 10, 页码 1469-1479

出版社

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1006/cyto.2000.0743

关键词

collagenase; cytokines; mitogen-activated protein kinases; nuclear factor-kappa B; transcription

资金

  1. NHLBI NIH HHS [HL52738] Funding Source: Medline
  2. NIAMS NIH HHS [AR02024] Funding Source: Medline
  3. NIEHS NIH HHS [ES07373] Funding Source: Medline

向作者/读者索取更多资源

Collagenase-1 (MMP-1) is a protease that is expressed by stromal cells and that is involved in remodeling of the extracellular matrix, IL-1 and TNF-alpha enhance collagenase secretion by stromal cells, and chronic exposure of cells to these cytokines can contribute to connective tissue disease. In this study, we show that the NF-kappaB pathway is required for activation of collagenase-1 transcription in rabbit primary synovial fibroblasts (RSF), Although both IL-1 and TNF activate NF-kappaB in these cells, only IL-1 induces collagenase-1 transcription. We have reported previously that NF-kappaB and AP-1 cooperate to mediate IL-1-induced MMP-1 transcription. Here, we show that IL-1 is superior to TNF at inducing c-Jun synthesis, phosphorylation and binding activity in RSP. Similarly, IL-l is more effective at activating the mitogen-activated protein kinases (MAPK), including the extracellular signal-regulated kinases (ERK), which are required for IL-l-induced MMP-1 transcription. Thus stimulation of the ERK and AP-1 pathways is an essential component of MMP-1 transcriptional activation, which is deficient in TNF-treated cells. These studies demonstrate cooperation between the MAPK and NF-kappaB Signaling pathways for IL-l-dependent collagenase-1 transcription, and they define a dichotomy of IL-1- and TNF-elicited signaling that is relevant to cytokine-mediated connective tissue disease. (C) 2000 Academic Press.

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