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Serum amyloid A triggers the mosodium urate -mediated mature interleukin-1β production from human synovial fibroblasts

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Title: Serum amyloid A triggers the mosodium urate -mediated mature interleukin-1β production from human synovial fibroblasts
Authors: Migita, Kiyoshi / Koga, Tomohiro / Satomura, Kenshi / Izumi, Masahiro / Torigoshi, Takafumi / Maeda, Yumi / Izumi, Yasumori / Jiuchi, Yuka / Miyashita, Taiichiro / Yamasaki, Satoshi / Aiba, Yoshihiro / Komori, Atsumasa / Nakamura, Minoru / Motokawa, Satoru / Kawakami, Atsushi / Nakamura, Tadashi / Ishibashi, Hiromi
Issue Date: 18-May-2012
Publisher: BioMed Central
Citation: Arthritis Research & Therapy, 14(3), R119; 2012
Abstract: Background: Monosodium urate (MSU) has been shown to promote inflammasome activation and interleukin-1β (IL-1β) secretion in monocyte/macrophages, but the cellular pathway and nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation in synovial tissues, remain elusive. In this study, we investigated the effects of MSU on synovial fibroblasts to elucidate the process of MSU-mediated synovial inflammation.Methods: Human synovial fibroblasts were stimulated with MSU in the presence or absence of serum amyloid A (SAA). The cellular supernatants were analyzed by immunoblotting using anti-IL-1β or anti-caspase-1 antibodies. IL-1β or NLRP3 mRNA expressions were analyzed by real-time PCR or reverse transcription-PCR (RT-PCR) method.Results: Neither SAA nor MSU stimulation resulted in IL-1β or interleukin-1α (IL-1α) secretions and pro-IL-1β processing in synovial fibroblasts. However, in SAA-primed synovial fibroblasts, MSU stimulation resulted in the activation of caspase-1 and production of active IL-1β and IL-1α. The effect of SAA on IL-1β induction was impaired in cells by silencing NLRP3 using siRNA or treating with caspase-1 inhibitor. In addition, SAA induced the secretion of cathepsin B and NLRP3 mRNA expression in synovial fibroblasts.Conclusions: Our data demonstrate that exposure of human synovial fibroblasts to SAA promotes MSU-mediated caspase-1 activation and IL-1β secretion in the absence of microbial stimulation. These findings provide insight into the molecular processes underlying the synovial inflammatory condition of gout.
Keywords: cathepsin B / cryopyrin / interleukin 1alpha / interleukin 1beta / messenger RNA / serum amyloid A / small interfering RNA / urate / article / controlled study / fibroblast / human / human cell / human tissue / immunoblotting / real time polymerase chain reaction / reverse transcription polymerase chain reaction / synovial fluid / synovitis
URI: http://hdl.handle.net/10069/29239
ISSN: 14786354
DOI: 10.1186/ar3849
Rights: © 2012 Migita et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/29239

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