title: Lipopolysaccharide upregulates the expression of corticotropin-releasing hormone via MAP kinase pathway in rat peritoneal macrophages.
abstract: 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.
authors.affiliation: Institute for Traffic Medicine, Research Institute of Surgery & Daping Hospital, Third Military Medical University, Daping, Chongqing, China.
authors.forename: Wuchao
authors.initials: W
authors.lastname: Wang
authors.forename: Xiuzhu
authors.initials: X
authors.lastname: Zhang
authors.forename: Lie
authors.initials: L
authors.lastname: Yang
authors.forename: Dawei
authors.initials: D
authors.lastname: Liu
authors.forename: Guodong
authors.initials: G
authors.lastname: Liu
authors.forename: Jihong
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
chemical_list: D005419:Flavonoids; D008070:Lipopolysaccharides; D003346:Corticotropin-Releasing Hormone; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one