Thrombin induces GRO alpha/MGSA production in human umbilical vein endothelial cells.
Thrombin, besides being a potent coagulation factor, exerts influence on endothelial and leukocyte functions and may thus be involved in the regulation of inflammatory reactions. The present study investigated whether thrombin stimulates the production of growth-related cytokine/melanoma growth-stimulatory activity (GRO alpha/MGSA) in endothelial cells. Human umbilical vein endothelial cells (HUVEC) stimulated with thrombin were found to product GRO alpha/MGSA in a dose- and time-dependent manner. This action of thrombin was completely suppressed by preincubation with either hirudin or antithrombin-III (AT-III)-heparin. Interestingly, the thrombin receptor-activating peptide SFLLRN mimicked the action of thrombin. In addition, staurosporine, a protein kinase C (PKC) inhibitor, attenuated the production of GRO alpha/MGSA by thrombin, SFLLRN and phorbol 12-myristate 13-acetate (PMA), but left the action of interleukin-1 beta (IL-1 beta) unchanged. These results suggest that catalytic activation of thrombin receptor by thrombin results in GRO alpha/MGSA production, at least in part, via a pathway involving PKC in HUVEC.
D000470:Alkaloids / Q000494:pharmacology; D000595:Amino Acid Sequence; D000990:Antithrombin III / Q000494:pharmacology; D002478:Cells, Cultured; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism*; D006133:Growth Substances / Q000096:biosynthesis*; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1 / Q000494:pharmacology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D018179:Receptors, Thrombin / Q000187:drug effects; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013917:Thrombin / Q000008:administration & dosage / Q000494:pharmacology*
D000470:Alkaloids; C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D006133:Growth Substances; D006629:Hirudins; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D010446:Peptide Fragments; D018179:Receptors, Thrombin; C082835:thrombin receptor peptide (42-47); D000990:Antithrombin III; D011493:Protein Kinase C; D013917:Thrombin; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate