title: Role of p38 MAPK in ICAM-1 expression of vascular endothelial cells induced by lipopolysaccharide.
abstract: Lipopolysaccharide (LPS) stimulation of endothelial cells induces the expression of intercellular adhesion molecule-1 (ICAM-1), a critical adhesion molecule involved in the adhesive interaction between leukocytes and endothelial cells in shock and inflammation. Although there is little literature about role of p38 mitogen-activated protein kinase (MAPK) in ICAM-1 protein expression of LPS-induced endothelial cells, it is still not defined whether gene transcription is regulated by p38 MAPK in ICAM-1 expression of LPS-induced endothelial cells. In this study, the potential role of p38 MAPK in ICAM-1 expression of LPS-induced endothelial cells was studied in vitro and in vivo. In vitro studies, the results showed that compared with basic expression of ICAM-1 protein on cultured human umbilical vein endothelial cells (HUVECs), the ICAM-1 expression was increased initially at 2 h after LPS stimulation, reached peak value at 24 h, and descended at 36 h obviously. A dose-dependent relationship existed between LPS concentration and ICAM-1 expression. The abundance of ICAM-1 mRNA in cytoplasma of endothelial cells was upregulated significantly by LPS stimulation at 2 h and was maintained at a high level from 4 to 36 h. The upregulation of ICAM-1 protein and mRNA expression of LPS-induced HUVECs was markedly inhibited by SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)imidazole], a highly specific inhibitor of p38 MAPK. Activity of p38 MAPK in HUVECs was increased at 15 min after LPS stimulation and reached the maximum at 60 min, then descended significantly. Activity of p38 MAPK was inhibited significantly by SB203580 in vitro. In vivo studies, administration of SB203580 (12.5 or 25 mg/kg, per ora) markedly reduced LPS-induced expression of ICAM-1 protein and mRNA of lung tissues of male BALB/c mice. These data highlight that the upregulation of ICAM-1 expression of LPS-induced endothelial cells in vitro and in vivo is mediated by p38 MAPK pathway at the level of gene transcription. The ICAM-1 expression of LPS-induced endothelial cells is characteristic of time dependence and dose dependence, and tolerates to chronic LPS stimulation. Inhibition of the p38 MAPK signal pathway may be used as an approach to attenuate ICAM-1 production in the treatment of septic shock.
authors.affiliation: Department of Pathophysiology, The First Military Medical University, Guangzhou, People's Republic of China.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Yan
authors.forename: Keseng
authors.initials: K
authors.lastname: Zhao
authors.forename: Yong
authors.initials: Y
authors.lastname: Jiang
authors.forename: Qiaobing
authors.initials: Q
authors.lastname: Huang
authors.forename: Jingzhen
authors.initials: J
authors.lastname: Wang
authors.forename: Wenhong
authors.initials: W
authors.lastname: Kan
authors.forename: Shiwen
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects; D012772:Shock, Septic / Q000139:chemically induced / Q000378:metabolism*; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D008070:Lipopolysaccharides; D011725:Pyridines; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580