CXCL12 gene expression is upregulated by hypoxia and growth arrest but not by inflammatory cytokines in rheumatoid synovial fibroblasts
CXCL12 gene expression is upregulated by hypoxia and growth arrest but not by inflammatory cytokines in rheumatoid synovial fibroblasts
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DOI：
10.1016/j.cyto.2010.06.006
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发表时间：
2011-02-01
期刊：
影响因子：
3.8
通讯作者：
Pablos, Jose L.
中科院分区：
文献类型：
--
作者：
Santiago, Begona;Calonge, Esther;Pablos, Jose L.
目的：CXCL12 是一种组成型表达的趋化因子，具有重要的稳态功能。在包括类风湿性关节炎 (RA) 在内的多种炎症性疾病中观察到 CXCL12 表达增加。本研究旨在确定正常或炎症条件下人类成纤维细胞调节 CXCL12 基因表达的潜在机制。方法：从 RA 和骨关节炎 (OA) 滑膜组织中培养滑膜成纤维细胞 (SF)。通过实时定量 RT-PCR 分析不同生长条件下、暴露于缺氧或不同促炎因子的 RA-SF 中 CXCL12 mRNA 的表达。将5'CXCL12 -1.4 kb启动子区片段克隆到荧光素酶报告质粒中，并在人成纤维细胞中分析其活性。结果：与OA-SF相比，RA-中CXCL12 mRNA表达没有组成型增加。 LPS、促炎细胞因子或生长因子不会诱导 SF 中 CXCL12 mRNA 的表达。缺氧和血清饥饿或汇合生长导致的生长停滞诱导 SF 中 CXCL12 mRNA 和蛋白表达。成纤维细胞中CXCL12的组成型和诱导型表达在转录水平上受到-1.4 kb启动子特定区域的调节。结论：促炎因子和细胞因子不会上调SF中CXCL12基因的表达。生长停滞和缺氧是人类成纤维细胞中 CXCL12 表达的潜在重要诱导物，并通过调节启动子的转录活性来发挥作用。 (C) 2010 Elsevier Ltd. 保留所有权利。
Objectives: CXCL12 is a constitutively expressed chemokine with important homeostatic functions. Increased CXCL12 expression has been observed in several inflammatory conditions, including rheumatoid arthritis (RA). This study was undertaken to identify potential mechanisms of regulation of CXCL12 gene expression by human fibroblasts under normal or inflammatory conditions.Methods: Synovial fibroblasts (SF) were cultured from RA and osteoarthritis (OA) synovial tissues. CXCL12 mRNA expression was analysed by real time quantitative RT-PCR in RA-SF under different growth conditions, and exposed to hypoxia or to different pro-inflammatory factors. A 5'CXCL12 -1.4 kb promoter region fragment was cloned in a luciferase reporter plasmid and its activity analysed in human fibroblasts.Results: CXCL12 mRNA expression was not constitutively increased in RA- compared to OA-SF. LPS, proinflammatory cytokines or growth factors did not induce CXCL12 mRNA expression in SF. Hypoxia and growth arrest by either serum starvation or confluent growth induced CXCL12 mRNA and protein expression in SF. Constitutive and induced expression of CXCL12 in fibroblasts was regulated at the transcriptional level by specific regions of the -1.4 kb promoter.Conclusions: Pro-inflammatory factors and cytokines do not up-regulate CXCL12 gene expression in SF. Growth arrest and hypoxia are potentially important inducers of CXCL12 expression in human fibroblasts and operate by regulating transcriptional activity of the promoter. (C) 2010 Elsevier Ltd. All rights reserved.