TNFa-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 TNFα-induced activation of endothelial adhesion molecules ICAM-1 and VCAM-1 was analysed. Phorbol myristate acetate, which is known to activate PKC, was able lo mimic TNFα-induced up-regulation of ICAM-1 and partly also VCAM-1 expression. Similarly a PKC inhibitor, H7, but not another kinase inhibitor. HA1004, inhibited TNFα-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 TNFα induction in endothelial cells analysed by phorbol-dibutyrate binding. These results indicate that the TNFα-induced effect on the regulation of endothelial adhesion molecule expression is at least partly mediated by PKC activation.