A pro-inflammatory role for A20 and ABIN family proteins in human fibroblast-like synoviocytes in rheumatoid arthritis

作者：Igarashi Hideya; Yahagi Ayano; Saika Taro; Hashimoto Jun; Tomita Tetsuya; Yoshikawa Hideki; Ishihara Katsuhiko^*

来源：Immunology Letters, 2012, 141(2): 246-253.

DOI：10.1016/j.imlet.2011.10.011

• Human fibroblast-like synoviocytes
• TNF alpha
• NF-kappa B
• A20
• ABINs

Circuit of chronic inflammation in the joints of rheumatoid arthritis (RA) starts from the production of inflammatory cytokines by fibroblast-like synoviocytes (FLS) stimulated by TNF alpha produced by inflammatory cells mainly composed of macrophages. In this context, TNF alpha/NF-kappa B pathway plays an essential role for the transcription of pro-inflammatory cytokines. Here we show that the kinetics of pro-inflammatory cytokine genes induced by TNF alpha in FLS from RA was synchronized with that of A20, ABIN1, and ABIN3 that have been thought as negative regulators for NF-kappa B activation. Furthermore, based on this finding, we could tentatively categorize the RA-FLS into two groups; TNF alpha low-responder and high-responder FLS. The high responders that have abundant mRNA levels of NF-kappa B inhibitory molecules were also accompanied with the marked induction of the pro-inflammatory cytokines by the stimulation with TNF alpha. The low responders RA-FLS did not show this property, nor did FLS from osteoarthritis. Phosphorylation dependent degradation of I kappa B alpha as well as NF-kappa B activation upon stimulation with TNF alpha was significantly enhanced in the high-responder FLS lines. Surprisingly, single transfection of each NF-kappa B inhibitor was enough to facilitate the transcription of pro-inflammatory cytokines, suggesting that there is an unknown pro-inflammatory function for A20 and ABIN family proteins in RA-FLS.

• 出版日期2012-1-30