Institute for Traffic Medicine, Research Institute of Surgery & Daping Hospital, Third Military Medical University, Daping, Chongqing, China.
Mol Cell Biochem. 2012 Feb;361(1-2):1-7. doi: 10.1007/s11010-011-1080-2. Epub 2011 Sep 30.
The stress neuropeptide, corticotropin-releasing hormone (CRH) is expressed in peripheral tissues and inflammatory sites and is implicated in the modulation of the inflammatory response in a paracrine/ autocrine manner. However, the mechanisms by which CRH expression is regulated in peripheral immune cells are unclear. In this article, we address this question by employing primary rat peritoneal macrophages treated with lipopolysaccharide (LPS). Our results showed that CRH could be detected at the mRNA and protein levels in normal peritoneal macrophages and the levels increased significantly and reached a peak at 4 h after stimulation with 100 ng/ml LPS. Furthermore, LPS-induced CRH expression was inhibited by pretreatment with PD98059, a specific MAP kinase inhibitor, in a dose-dependent fashion in which the mRNA and protein levels of CRH was decreased by 90% and 95%, respectively. In addition, pretreatment with 50 μM SB203580, a p38 MAPK inhibitor, led to the decrease of CRH mRNA level by about 41%. Altogether, these results demonstrate that LPS significantly upregulates CRH expression through MAP kinase signaling pathway in rat peritoneal macrophages.
应激神经肽，促肾上腺皮质释放激素（CRH）在周围组织和炎症部位表达，并通过旁分泌/自分泌方式参与调节炎症反应。然而，CRH 在周围免疫细胞中的表达是如何调节的机制尚不清楚。在本文中，我们通过使用脂多糖（LPS）处理的原代大鼠腹腔巨噬细胞来解决这个问题。我们的结果表明，CRH 可在正常腹腔巨噬细胞的 mRNA 和蛋白水平上检测到，并且在 100ng/ml LPS 刺激后 4 小时显着增加并达到峰值。此外，用 PD98059（一种特定的 MAP 激酶抑制剂）预处理可抑制 LPS 诱导的 CRH 表达，呈剂量依赖性，其中 CRH 的 mRNA 和蛋白水平分别降低 90%和 95%。此外，用 p38 MAPK 抑制剂 SB203580（50μM）预处理可导致 CRH mRNA 水平降低约 41%。总之，这些结果表明 LPS 通过大鼠腹腔巨噬细胞中的 MAP 激酶信号通路显着上调 CRH 表达。
