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Open Access Research article

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

Kiyoshi Migita13*, Tomohiro Koga4, Kenshi Satomura12, Masahiro Izumi12, Takafumi Torigoshi12, Yumi Maeda3, Yasumori Izumi1, Yuka Jiuchi3, Taiichiro Miyashita1, Satoshi Yamasaki4, Yoshihiro Aiba3, Atsumasa Komori3, Minoru Nakamura3, Satoru Motokawa12, Atsushi Kawakami4, Tadashi Nakamura5 and Hiromi Ishibashi3

Author affiliations

1 Department of Rheumatology, Nagasaki Medical Center, Kubara 2-1001-1, Omura, Nagasaki 856-8562, Japan

2 Orthopedic Surgery, Nagasaki Medical Center, Kubara 2-1001-1, Omura, Nagasaki 856-8562, Japan

3 Clinical Research Center, Nagasaki Medical Center, Kubara 2-1001-1, Omura, Nagasaki 856-8562, Japan

4 Department of Rheumatology, Nagasaki University Hospital, Sakamoto 1-7-1, Nagasaki 852-8201, Japan

5 Department of Rheumatology, NTT West Japan Hospital, Shinyashiki 1-17 Kumamoto 862-8655, Japan

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Citation and License

Arthritis Research & Therapy 2012, 14:R119  doi:10.1186/ar3849

Published: 18 May 2012



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.


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.


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.


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.