INHIBITORY EFFECTS OF PROTEIN KINASE C INHIBITORS ON TUMOR NECROSIS FACTOR INDUCED BOVINE PULMONARY ARTERY ENDOTHELIAL CELL INJURIES

The effects of protein kinase C(PKC)inhibitors 1-(5-isoquino-linylsulfonyl)-2-methylpeperazine(H-7)and quercetin on tumor necrosis factor(TNF)were studied in cuItured bevinepulmonary artery endothelial cells(BPAEC) in vitro. Incubation of BPAEC with TNF caused a signifi-cant increase in percent lactate dehydrogenase(LDH)release,stimulation of EC-dependent neutrophils(PMN)adhesion to BPAEC and inhibition of BPAEC DNA synthesis and proliferation. All these wererestored by both H-7 and quercetin,The IC₅₀ of H-7 and quercetin was 9.7 and 10.8 μmol·L^-1 forthe inhibition of LDH%release;19.5 and 16.7μmol·L^-1 for the inhibition of TNF-induced PMN-EC adhesion;7.0 and 6.1 μmol · L^-1 for TNF-induced inhibition of DNA synthesis and 8.7 and11.36 μmol·L^-1 for proliferation.These results suggest that PKC inhibitors H-7 and quercetinprotect BPAEC from TNF induced injuries and PKC play an important role in EC activation by TNF.