The Role Of P38 MAPK In LPS-induced ICAM-1 Expression Of Vascular Endothelial Cells

Intercellular adhesion molecule-i (ICAM- 1) is a critical adhesion molecule existing on vascular endothelial cells, which promotes circulatory leukocytes adhering to endothelial cells and mediates stagnation of microcirculation and deterioration of shock, in shock and inflammation induced by lipopolysaccharide(LPS). Though there was one literature about p38 mitogen-activated protein kinase(MAPK) involed in regulation of LPS-induceed ICAM- 1 protein expression of endothelial cells, it was still not clear that whether protein translation or gene transcription was regulated by p38 MAPK in LPS-induced ICAM-1 expression. In this paper, the potential role of p38 MAPK in LPS-induced ICAM-1 expression of human umbilical vein endothelial cells (HUVEC) was studied. For this purpose, we measured dynamic changes of ICAM- 1 protein and mRNA of HUVEC treated by LPS and p38 MAPK specific inhibitor SB203580 by cellular immune fluorescent staining and laser confocal microscope and reverse transcription-polymerase chain reaction(RT-PCR), and we also measured activity of p38 MAPK by immunoprecipitation and autoradiography. The results showed that, compareing with basic expression of ICAM-i on HUVEC, the ICAM- 1 expression was increased initially at 2h after LPS stimulation, reached peak value from I 2h to 24h, and then descended obviously. Dose-dependent relationship existed between LPS and ICAM-1 expression. The abundance of ICAM-1 mRNA in cytoplasma was up-regulated significantly at 2h, and maintained high level from 4h to 36h. The stimulating role of LPS to expression of protein and mRNA of ICAM-1 of HUVEC was markedly inhibited by SB203580. Activity of p38 MAPK in HUVEC treated by LPS was increased at 15mm and reached maximum value during 30- 60min,then decended. Activity of p38 MAPK was inhibited significantly by SB203580 in vitro. We concluded that the upregulation of ICAM- 1 expression of endothelial cells stimulated by LPS was mediated by p38 MAPK pathway in the level of gene transcription. LPS-induced ICAM- 1 expression of endothelial cells possessed time- dependent and dose-dependent characteristics, and tolerated to LPS chronical stimulation.