The effects of inflammatory cytokines on steroidogenic acute regulatory protein expression in macrophages
The effects of inflammatory cytokines on steroidogenic acute regulatory protein expression in macrophages
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DOI：
10.1007/s00011-007-6133-3
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发表时间：
2007-12-01
影响因子：
6.7
通讯作者：
Yin, L.
中科院分区：
文献类型：
--
作者：
Ma, Y.;Ren, S.;Yin, L.
目的：探讨巨噬细胞中类固醇急性调节蛋白（steroids ogenic acute regulatory protein, StAR）的表达及炎症因子对其表达的影响。方法：从ApoE敲除小鼠和C57BL/6J小鼠中分离巨噬细胞和小鼠巨噬细胞RAW264.7细胞系。ATCC编号：TIB-71 (TM))在含有10%胎牛血清的DMEM中培养。RAW264.7细胞用不同的炎症因子（tnf - α、ifn - γ和tgf - β 1）和8-Br-cAMP（一种cAMP类似物）处理。采用RT-PCR和Western blot分析炎症因子对StAR表达的影响。结果：RT-PCR和Western blot分析显示，ApoE敲除小鼠、C57BL/6J小鼠和RAW264.7细胞分离的巨噬细胞中均有StAR的表达。促炎细胞因子tnf - α和ifn - γ显著降低RAW264.7细胞中StAR mRNA和蛋白水平。抑制作用具有剂量和时间依赖性。相反，抗炎细胞因子tgf - β 1增加了StAR mRNA和蛋白水平。在1:15分子比下，tgf - β 1阻断了tnf - α介导的StAR表达下调。cAMP还能诱导RAW264.7细胞中StAR的表达。当细胞与8-Br-cAMP和tnf - α共处理时，8-Br-cAMP不能诱导StAR表达。结论：我们的研究结果提供了炎症因子调节巨噬细胞StAR表达的有趣证据。
Objective: To investigate the expression of steroidogenic acute regulatory protein (StAR) in macrophages and the effects of inflammatory cytokines on StAR expression.Methods: The macrophages isolated from ApoE knockout mice and C57BL/6J mice and RAW264.7 cells (a cell line from mouse macrophage. ATCC Number: TIB-71 (TM)) were cultured in DMEM containing 10% fetal bovine serum. RAW264.7 cells were treated with different inflammatory cytokines (TNF-alpha, IFN-gamma and TGF-beta 1) and 8-Br-cAMP, a cAMP analog. RT-PCR and Western blot analysis were applied to evaluate the effects of inflammatory cytokines on StAR expression.Results: RT-PCR and Western blot analysis demonstrated the expression of StAR in the macrophages isolated from ApoE knockout mice, C57BL/6J mice and RAW264.7 cells. Pro-inflammatory cytokines TNF-alpha and IFN-gamma significantly decreased StAR mRNA and protein levels in RAW264.7 cells. The inhibition was dose- and time-dependent. In contrast, anti-inflammatory cytokine TGF-beta 1 increased StAR mRNA and protein levels. At 1: 15 molecular ratio, TGF-beta 1 blocked the down-regulation of StAR expression mediated by TNF-alpha. cAMP also induced StAR expression in RAW264.7 cells. When the cells were co-treated with 8-Br-cAMP and TNF-alpha, 8-Br-cAMP failed to induce StAR expression.Conclusion: Our results provide interesting evidence that inflammatory cytokines regulate StAR expression in macrophages.