@article{oai:nagasaki-u.repo.nii.ac.jp:00010688,
 author = {Migita, Kiyoshi and Koga, Tomohiro and Satomura, Kenshi and Izumi, Masahiro and Torigoshi, Takafumi and Maeda, Yumi and Izumi, Yasumori and Jiuchi, Yuka and Miyashita, Taiichiro and Yamasaki, Satoshi and Aiba, Yoshihiro and Komori, Atsumasa and Nakamura, Minoru and Motokawa, Satoru and Kawakami, Atsushi and Nakamura, Tadashi and Ishibashi, Hiromi},
 issue = {3},
 journal = {Arthritis Research & Therapy},
 month = {May},
 note = {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., Arthritis Research & Therapy, 14(3), R119; 2012},
 title = {Serum amyloid A triggers the mosodium urate -mediated mature interleukin-1β production from human synovial fibroblasts},
 volume = {14},
 year = {2012}
}