Department of Anesthesiology

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Cross-talk between IL-1 and IL-6 signaling pathways in rheumatoid arthritis synovial fibroblasts.

TitleCross-talk between IL-1 and IL-6 signaling pathways in rheumatoid arthritis synovial fibroblasts.
Publication TypeJournal Article
Year of Publication2001
AuthorsDeon D, Ahmed S, Tai K, Scaletta N, Herrero C, Lee IH, Krause A, Ivashkiv LB
JournalJ Immunol
Volume167
Issue9
Pagination5395-403
Date Published2001 Nov 1
ISSN0022-1767
KeywordsArthritis, Rheumatoid, DNA-Binding Proteins, Fibroblasts, Humans, Interleukin-1, Interleukin-6, Mitogen-Activated Protein Kinases, Receptors, Interleukin-6, Signal Transduction, STAT1 Transcription Factor, STAT3 Transcription Factor, Synovial Membrane, Trans-Activators, Tumor Necrosis Factor-alpha
Abstract

The balance between pro- and anti-inflammatory cytokines plays an important role in determining the severity of inflammation in rheumatoid arthritis (RA). Antagonism between opposing cytokines at the level of signal transduction plays an important role in many other systems. We have begun to explore the possible contribution of signal transduction cross-talk to cytokine balance in RA by examining the effects of IL-1, a proinflammatory cytokine, on the signaling and action of IL-6, a pleiotropic cytokine that has both pro- and anti-inflammatory actions, in RA synovial fibroblasts. Pretreatment with IL-1 suppressed Janus kinase-STAT signaling by IL-6, modified patterns of gene activation, and blocked IL-6 induction of tissue inhibitor of metalloproteases 1 expression. These results suggest that proinflammatory cytokines may contribute to pathogenesis by modulating or blocking signal transduction by pleiotropic or anti-inflammatory cytokines. The mechanism of inhibition did not require de novo gene activation and did not depend upon tyrosine phosphatase activity, but, instead, was dependent on the p38 stress kinase. These results identify a molecular basis for IL-1 and IL-6 cross-talk in RA synoviocytes and suggest that, in addition to levels of cytokine expression, modulation of signal transduction also plays a role in regulating cytokine balance in RA.

Alternate JournalJ. Immunol.
PubMed ID11673558