血清淀粉样蛋白A可刺激类风湿性滑膜细胞产生CCL20。

Serum amyloid A protein stimulates CCL20 production in rheumatoid synoviocytes.

作者信息

Migita Kiyoshi, Koga Tomohiro, Torigoshi Takafumi, Maeda Yumi, Miyashita Taichiro, Izumi Yasumori, Aiba Yoshihiro, Komori Atsumasa, Nakamura Minoru, Motokawa Satoru, Ishibashi Hiromi

机构信息

Department of Rheumatology, Clinical Research Center, NHO Nagasaki Medical Center, Omura, Japan.

出版信息

Rheumatology (Oxford). 2009 Jul;48(7):741-7. doi: 10.1093/rheumatology/kep089. Epub 2009 May 15.

DOI:10.1093/rheumatology/kep089

PMID:19447772

Abstract

OBJECTIVE

Although serum amyloid A (SAA) has been used as a marker of inflammation, its role in leucocyte recruitment and angiogenesis has not been well established in RA. CCL20 is a chemokine involved in the migration of CCR6-expressing Th17 cells. To study the contribution of SAA to the recruitment of Th17 cells, we investigated the effects of SAA on CCL20 production by RA synoviotytes.

METHODS

Synoviocytes isolated from RA patients were stimulated with recombinant SAA and cellular supernatants were analysed by CCL20-specific ELISA. CCL-20 mRNA expression was analysed by RT-PCR.

RESULTS

SAA is a most potent inducer of CCL20 secretion in RA synoviocytes compared with other inflammatory cytokines (IL-1beta, TNF-alpha and IL-17A). SAA stimulation induced CCL20 mRNA expression in RA synoviocytes, which was not affected by polymyxin B pre-treatment. SAA-induced CCL20 production was down-regulated by NF-kappaB inhibition and partially by c-jun N-terminal kinase (JNK) inhibition. SAA-induced CCL20 production was also suppressed by dexamethasone or FK506.

CONCLUSION

These findings suggest that SAA may be implicated in the recruitment of lymphocytes, including CCR6-expressing Th17 cells, in RA synovium by up-regulating CCL20 production in synoviocytes.

摘要

目的

尽管血清淀粉样蛋白A（SAA）已被用作炎症标志物，但其在类风湿关节炎（RA）中白细胞募集和血管生成中的作用尚未完全明确。CCL20是一种趋化因子，参与表达CCR6的Th17细胞的迁移。为了研究SAA在Th17细胞募集中的作用，我们调查了SAA对RA滑膜细胞产生CCL20的影响。

方法

用重组SAA刺激从RA患者分离的滑膜细胞，并用CCL20特异性ELISA分析细胞上清液。通过RT-PCR分析CCL-20 mRNA表达。

结果

与其他炎性细胞因子（IL-1β、TNF-α和IL-17A）相比，SAA是RA滑膜细胞中CCL20分泌的最有效诱导剂。SAA刺激诱导RA滑膜细胞中CCL20 mRNA表达，这不受多粘菌素B预处理的影响。SAA诱导的CCL20产生通过抑制NF-κB而下调，部分通过抑制c-jun N端激酶（JNK）而下调。地塞米松或FK506也可抑制SAA诱导的CCL20产生。