Tumor necrosis factor decreases thrombin receptor expression in endothelial cells

Journal of Cellular Physiology
W YanA B Malik

Abstract

We examined the effects of the proinflammatory cytokine, tumor necrosis factor-alpha (TNF alpha) on the expression of proteolytically activated thrombin receptor (PATR) in human umbilical vein endothelial cells (HUVEC). PATR mRNA and protein levels were measured in confluent HUVEC monolayers after challenge with TNF alpha. Northern analysis indicated that TNF alpha treatment resulted in 2- to 3-fold decrease in PATR mRNA in a time- and dose-dependent manner. PATR mRNA level returned to the control level within 6 hr. The nuclear run-on assay indicated that the decreased mRNA signal was due to reduction in the transcription rate. Immunoblotting experiments indicated that the decrease in expression of PATR protein followed in time the decrease in mRNA; the lowest level of protein expression was achieved at 22 hr after TNF alpha treatment. PATR protein returned to basal value within 40 hr after TNA alpha challenge. To assess alterations in endothelial cell function after TNF alpha treatment, we measured thrombin-induced increase in cytosolic Ca2+ ([Ca2+]i) and the cell shape change (measured by decrease in electrical impedance of endothelial cell monolayer). In HUVEC treated with TNF alpha (100 U/ml for 22 hr), the rise in [Ca2+]i ...Continue Reading

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Citations

Oct 10, 2001·Springer Seminars in Immunopathology·M E Taekema-RoelvinkM R Daha
Jun 27, 2007·Immunology and Cell Biology·Huiyun ZhangShaoheng He
Jan 4, 2005·Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology·Yukiyo YamamotoTakashi Yoshiki
Jun 22, 2000·Proceedings of the National Academy of Sciences of the United States of America·C TiruppathiA B Malik
Jan 19, 2005·Journal of Pharmacological Sciences·Katsuya HiranoHideo Kanaide
Nov 11, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Katsuya Hirano
Dec 24, 2005·Physiological Reviews·Dolly Mehta, Asrar B Malik
Sep 13, 2019·Scientific Reports·Marion AvrilJoseph D Smith
Feb 13, 2001·Experimental Cell Research·C MbebiM Verdière-Sahuqué
Apr 7, 2000·Journal of the American Society of Nephrology : JASN·Miriam E J Taekema-RoelvinkMohamed R Daha

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