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

Serum amyloid A triggers the mosodium urate -mediated mature interleukin-1β production from human synovial fibroblasts - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Arthritis Research and Therapy

, 14:R119

First Online: 18 May 2012Received: 28 December 2011Revised: 04 April 2012Accepted: 18 May 2012


BackgroundMonosodium 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.

MethodsHuman 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.

ResultsNeither 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.

ConclusionsOur 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.

AbbreviationsATPadenosine triphosphate

ASCapoptosis-associated speck-like protein containing CARD


NLRP3Nod-like receptor family: pyrin domain containing 3

MSUmonosodium urate

SAAserum amyloid A

TLRtoll-like receptor.

Electronic supplementary materialThe online version of this article doi:10.1186-ar3849 contains supplementary material, which is available to authorized users.

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Autor: Kiyoshi Migita - Tomohiro Koga - Kenshi Satomura - Masahiro Izumi - Takafumi Torigoshi - Yumi Maeda - Yasumori Izumi - Yuka


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