Inhibition of TNF-induced IL-6 by the TWEAK-Fn14 interaction in rheumatoid arthritis fibroblast like synoviocytes

Jiro Yamana, Eric Morand, Tsuno Manabu, Katsue Sunahori, Kouji Takasugi, Hirofumi Makino, Masahiro Yamamura

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TNF-like weak inducer of apoptosis (TWEAK), a member of the TNF superfamily, has been shown to increase cytokine production by rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). In this study, we determined the effect of interaction between TWEAK and its receptor fibroblast growth factor-inducible-14 (Fn14) on cytokine expression in RAFLS. METHODS: RAFLS were obtained from surgical synovial specimens and used at passage 5-10. Cytokine protein and mRNA expression were measured with ELISA and real time-PCR, respectively. Apoptotic cells were detected by TUNEL assay. RelB activation was detected by Western blot analysis. RESULTS: TWEAK inhibited IL-6 production from total synovial cells from RA. TWEAK weakly induced FLS IL-6 and IL-8, but in contrast TWEAK dose-dependently inhibited IL-6 and IL-8 production by TNFI?-activated FLS. TWEAK did not induce apoptosis in FLS but inhibited proliferation of TNFI?-activated FLS. TWEAK induced RelB activation and suppressed IL-6 mRNA expression in TNFI?-activated FLS and both of these phenomenon were abolished by inhibition of new protein synthesis with cycloheximide.
Original languageEnglish
Pages (from-to)293 - 298
Number of pages6
JournalCellular Immunology
Issue number2
Publication statusPublished - 2012

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