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.
Mattila
P
P
Department of Bacteriology and Immunology, University of Helsinki, Finland.
Majuri
M L
ML
Mattila
P S
PS
Renkonen
R
R
D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000032:analysis*; D004730:Endothelium, Vascular / Q000737:chemistry*; D004789:Enzyme Activation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate