Reference - Detail
|Author||Igarashi H, Yahagi A, Saika T, Hashimoto J, Tomita T, Yoshikawa H, Ishihara K.|
|Title||A pro-inflammatory role for A20 and ABIN family proteins in human fibroblast-like synoviocytes in rheumatoid arthritis.|
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 TNFα produced by inflammatory cells mainly composed of macrophages. In this context, TNFα/NF-κB 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 TNFα in FLS from RA was synchronized with that of A20, ABIN1, and ABIN3 that have been thought as negative regulators for NF-κB activation. Furthermore, based on this finding, we could tentatively categorize the RA-FLS into two groups; TNFα low-responder and high-responder FLS. The high responders that have abundant mRNA levels of NF-κB inhibitory molecules were also accompanied with the marked induction of the pro-inflammatory cytokines by the stimulation with TNFα. The low responders RA-FLS did not show this property, nor did FLS from osteoarthritis. Phosphorylation dependent degradation of IκBα as well as NF-κB activation upon stimulation with TNFα was significantly enhanced in the high-responder FLS lines. Surprisingly, single transfection of each NF-κB 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.
|MeSH||Arthritis, Rheumatoid / immunology* Cells, Cultured DNA-Binding Proteins / genetics DNA-Binding Proteins / immunology DNA-Binding Proteins / metabolism* Fibroblasts / immunology Fibroblasts / metabolism* Fibroblasts / pathology Humans Inflammation Inflammation Mediators / metabolism Interleukin-1beta / genetics Interleukin-1beta / immunology Interleukin-1beta / metabolism Interleukin-6 / genetics Interleukin-6 / immunology Interleukin-6 / metabolism Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / immunology Intracellular Signaling Peptides and Proteins / metabolism* NF-kappa B / immunology NF-kappa B / metabolism Nuclear Proteins / genetics Nuclear Proteins / immunology Nuclear Proteins / metabolism* Proteins / genetics Proteins / immunology Proteins / metabolism* Signal Transduction / immunology Synovial Membrane / pathology Transcriptional Activation / genetics Transgenes / genetics Tumor Necrosis Factor alpha-Induced Protein 3 Tumor Necrosis Factor-alpha / immunology Tumor Necrosis Factor-alpha / metabolism|
|Human and Animal Cells||MH7A (RCB1512)|