TY - JOUR
T1 - Inhibition of TNF-induced IL-6 by the TWEAK-Fn14 interaction in rheumatoid arthritis fibroblast like synoviocytes
AU - Yamana, Jiro
AU - Morand, Eric
AU - Manabu, Tsuno
AU - Sunahori, Katsue
AU - Takasugi, Kouji
AU - Makino, Hirofumi
AU - Yamamura, Masahiro
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
UR - http://www.sciencedirect.com/science/article/pii/S0008874911002371
U2 - 10.1016/j.cellimm.2011.09.004
DO - 10.1016/j.cellimm.2011.09.004
M3 - Article
SN - 0008-8749
VL - 272
SP - 293
EP - 298
JO - Cellular Immunology
JF - Cellular Immunology
IS - 2
ER -