| A pro-inflammatory role for A20 and ABIN family proteins in human fibroblast-like synoviocytes in rheumatoid arthritis. | |
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MedLine Citation:
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PMID: 22093807 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Hideya Igarashi; Ayano Yahagi; Taro Saika; Jun Hashimoto; Tetsuya Tomita; Hideki Yoshikawa; Katsuhiko Ishihara |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-9 |
Journal Detail:
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Title: Immunology letters Volume: - ISSN: 1879-0542 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7910006 Medline TA: Immunol Lett Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier B.V. |
Affiliation:
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Department of Immunology and Molecular Genetics, Kawasaki Medical School, 577 Matsushima, Kurashiki City, Okayama 701-0192, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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