title: Role of tyrosine kinase enzymes in TNF-alpha and IL-1 induced expression of ICAM-1 and VCAM-1 on human umbilical vein endothelial cells.
abstract: The aim of this study was to analyse the potential roles of protein kinase enzymes in tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) induced expression of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on human umbilical vein endothelial cells (HUVEC). The authors observed a marked increase in ICAM-1 and VCAM-1 expression on HUVEC stimulated for 24 h by TNF-alpha (10 ng/ml) or IL-1 (20 ng/ml). Pre-treatment of HUVEC for 30 min with protein tyrosine kinase (PTK) inhibitors genistein and herbimycin A (10 micrograms/ml and 0.5 microgram/ml, respectively) before stimulation with IL-1 did not affect the expression of these molecules. Similar results were observed with respect to VCAM-1 expression on HUVEC stimulated by TNF-alpha. In contrast, pre-incubation of HUVEC with PTK inhibitors prior to the addition of TNF-alpha significantly enhanced subsequent expression of ICAM-1, although spontaneous expression of ICAM-1 on unstimulated HUVEC was unaffected. Western blot analysis demonstrated a significant increase in phosphorylated tyrosine protein levels in HUVEC stimulated by TNF-alpha, and significantly lower levels of these proteins in TNF-alpha stimulated HUVEC pre-treated with PTK inhibitors. These results demonstrate that IL-1 induced ICAM-1 and VCAM-1 expression does not result from activation of PTK-dependent pathways. In the case of TNF-alpha induced responses, the selective co-stimulatory effect of this cytokine in combination with PTK inhibitors on ICAM-1 expression suggests a complicated intracellular pathway of TNF-alpha induced ICAM-1 expression, possibly involving down-modulation of increases in ICAM-1 by PTK enzymes.
authors.affiliation: Department of Pathophysiology, Military Medical Academy, Lódz, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Majewska
authors.forename: E
authors.initials: E
authors.lastname: Paleolog
authors.forename: Z
authors.initials: Z
authors.lastname: Baj
authors.forename: U
authors.initials: U
authors.lastname: Kralisz
authors.forename: M
authors.initials: M
authors.lastname: Feldmann
authors.forename: H
authors.initials: H
authors.lastname: Tchórzewski
mesh_terms: D016227:Benzoquinones; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000494:pharmacology*; D007529:Isoflavones / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
chemical_list: D016227:Benzoquinones; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D007529:Isoflavones; D047029:Lactams, Macrocyclic; D011809:Quinones; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D017828:Rifabutin; C020754:herbimycin; D019833:Genistein; D011505:Protein-Tyrosine Kinases