A pro-inflammatory role for A20 and ABIN family proteins in human fibroblast-like synoviocytes in rheumatoid arthritis
| Autor: | Taro Saika, Hideki Yoshikawa, Jun Hashimoto, Ayano Yahagi, Katsuhiko Ishihara, Hideya Igarashi, Tetsuya Tomita |
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| Rok vydání: | 2012 |
| Předmět: |
Transcriptional Activation
musculoskeletal diseases Interleukin-1beta Immunology Arthritis Inflammation Biology Proinflammatory cytokine Arthritis Rheumatoid chemistry.chemical_compound medicine Humans Immunology and Allergy Transgenes skin and connective tissue diseases Cells Cultured Tumor Necrosis Factor alpha-Induced Protein 3 Interleukin-6 Tumor Necrosis Factor-alpha Synovial Membrane Intracellular Signaling Peptides and Proteins NF-kappa B Nuclear Proteins Proteins NF-κB Transfection Fibroblasts musculoskeletal system medicine.disease DNA-Binding Proteins IκBα chemistry Cancer research Tumor necrosis factor alpha Inflammation Mediators medicine.symptom Signal Transduction |
| Zdroj: | Immunology Letters. 141:246-253 |
| ISSN: | 0165-2478 |
| DOI: | 10.1016/j.imlet.2011.10.011 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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