TNF alpha-induced expression of endothelial adhesion molecules, ICAM-1 and VCAM-1, is linked to protein kinase C activation.

The role of protein kinase C (PKC) in TNF alpha-induced activation of endothelial adhesion molecules ICAM-1 and VCAM-1 was analysed. Phorbol myristate acetate, which is known to activate PKC, was able to mimic TNF alpha-induced up-regulation of ICAM-1 and partly also VCAM-1 expression. Similarly a PKC inhibitor, H7, but not another kinase inhibitor, HA1004, inhibited TNF alpha-induced enhancement of ICAM-1 expression at both the mRNA and the protein level. Moreover we were able to measure a transient PKC activation peak at 16 min after TNF alpha induction in endothelial cells analysed by phorbol-dibutyrate binding. These results indicate that the TNF alpha-induced effect on the regulation of endothelial adhesion molecule expression is at least partly mediated by PKC activation.