PROTEIN-TYROSINE-KINASE-DEPENDENT EXPRESSION OF CYCLO-OXYGENASE-1 ANDCYCLO-OXYGENASE-2 MESSENGER-RNA IN HUMAN ENDOTHELIAL-CELLS

Endothelial cells possess constitutive or inducible cycle-oxygenase (C OX) isoenzymes for prostacyclin production, but the mechanisms for the ir expression are largely unknown. We found that vanadate, an inhibito r of protein-tyrosine phosphatases, induced the expression of two COX isoenzyme mRNAs in human umbilical vein endothelial cells (HWEC) in a time- and dose-dependent manner. Vanadate also stimulated an increase in COX-2 protein levels, but did not affect significantly the levels o f constitutively expressed COX-1 protein. Synergistic enhancement of e xpression of the two COX isoenzyme mRNAs was observed on stimulation o f HUVEC with vanadate plus interleukin-1 alpha. Tyrphostin-47, which a s an inhibitor of protein-tyrosine kinases abolished vanadate-induced protein-tyrosine phosphorylation, inhibited expression of the two COX isoenzyme mRNAs in HUVEC stimulated with vanadate or interleukin-la. T hese data provide conclusive evidence that activation of protein-tyros ine kinases is causally linked to expression of the mRNAs for the two COX isoenzymes in HUVEC.