Post-transcriptional regulation of IL-6 production by Zc3h12a in fibroblast-like synovial cells.
Post-transcriptional regulation of IL-6 production by Zc3h12a in fibroblast-like synovial cells.
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发表时间：
2011-11
影响因子：
3.7
通讯作者：
T. Koga;S. Yamasaki;K. Migita;J. Kita;A. Okada;S. Kawashiri;N. Iwamoto;M. Tamai;K. Arima;T. Origuchi;Hideki Nakamura;M. Osaki;T. Tsurumoto;H. Shindo;K. Eguchi;A. Kawakami
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作者：
T. Koga;S. Yamasaki;K. Migita;J. Kita;A. Okada;S. Kawashiri;N. Iwamoto;M. Tamai;K. Arima;T. Origuchi;Hideki Nakamura;M. Osaki;T. Tsurumoto;H. Shindo;K. Eguchi;A. Kawakami
Zc 3 h12 a是一种具有CCCH型指状基序的RNA结合蛋白，已知可调节mRNA代谢。以前的报道表明，Zc 3 h12 a作为炎症过程的负调节剂，因为它参与了IL-6 mRNA的降解。我们研究了Zc 3 h12 a对类风湿关节炎（RA）患者成纤维细胞样滑膜细胞（FLS）产生IL-6的影响。方法采用聚合酶链反应（PCR）检测Zc 3 h12 a在FLS中的表达。为了敲低FLS中Zc 3 h12 a的表达，通过脂质体转染法转染针对Zc 3 h12 a的siRNA。在siRNA转染后收集上清液用于定量IL-6产生。Western blotting检测细胞内信号转导和转录激活因子3（STAT 3）的磷酸化水平。在Zc 3 h12 a敲低后通过Cell Counting Kit-8测定分析细胞增殖。结果Zc 3 h12 a mRNA在RA患者FLS中表达。LPS或IL-1β可诱导FLS中Zc 3 h12 a的转录。Zc 3 h12 a基因敲低可显著增加IL-6的产生及其mRNA表达。Zc 3 h12 a敲除还诱导STAT 3的激活，而抗IL-6受体抗体则抑制了STAT 3的激活。在重组可溶性IL-6受体（sIL-6 R）的存在下，Zc 3 h12 a敲低的FLS的增殖显著增加。结论Zc 3 h12 a是FLS中一种新的IL-6调节因子，可能参与RA的发生发展。
OBJECTIVES Zc3h12a is an RNA binding protein with a CCCH-type finger motif and is known to regulate mRNA metabolism. Previous reports suggest that Zc3h12a acts as a negative regulator of inflammatory processes because it is involved in the degradation of IL-6 mRNA. We investigate the effect of Zc3h12a on IL-6 production in fibroblast-like synovial cells (FLS) from rheumatoid arthritis (RA) patients. METHODS The expression of Zc3h12a in FLS was determined by polymerase chain reaction. To knock down Zc3h12a expression in FLS, siRNA for Zc3h12a was transfected by the lipofection method. The supernatants were collected after siRNA transfection for the quantification of IL-6 production. The phosphorylation of the signal transducer and activator of transcription 3 (STAT3) was examined by Western blotting. Cell proliferation was analysed by the Cell Counting Kit-8 assay after Zc3h12a knockdown. RESULTS mRNA for Zc3h12a were demonstrated in FLS from RA patients. Zc3h12a transcripts were induced by LPS or IL-1β in FLS. The production of IL-6 as well as its mRNA expression was significantly increased by the Zc3h12a knockdown. The Zc3h12a knockdown also induced the activation of STAT3, which the anti IL-6 receptor antibody inhibited. Proliferation of Zc3h12a-knockdown FLS increased significantly in the presence of recombinant soluble IL-6 receptor (sIL-6R). CONCLUSIONS Our data suggest that Zc3h12a is a novel IL-6 regulator in FLS, which may be involved in the progression of RA.