P38 MITOGEN-ACTIVATED PROTEIN-KINASE REGULATES ENDOTHELIAL VCAM-1 EXPRESSION AT THE POSTTRANSCRIPTIONAL LEVEL

The cytokine tumor necrosis factor (TNF) alpha was found to stimulate the p38 mitogen activated protein (MAP) kinase signalling cascade in h uman umbilical vein endothelial cells. TNF alpha increased the activit y of the p38 substrate MAP kinase-activated-protein (MAPK-KAP) kinase 2 and the subsequent phosphorylation of the small heat shock protein H sp27 about two to three fold. This stimulation was blocked almost comp letely by the specific p38 MAP kinase inhibitor SB203580. This inhibit or also suppressed the TNF alpha-induced surface expression of the end othelial adhesion molecule vascular cell adhesion molecule (VCAM)-1. I n contrast, inhibition of p38 MAP kinase had no effect on the stimulat ed surface expression of the intercellular cell adhesion molecule (ICA M)-1. VCAM-1 mRNA accumulation induced by TNF alpha was not affected b y SB203580, suggesting that the p38 MAP kinase signalling cascade regu lates the endothelial expression of VCAM-1 at the post-transcriptional level. (C) 1997 Academic Press