Activation of p42mapk in human umbilical vein endothelial cells by interleukin-1 alpha and tumor necrosis factor-alpha

The American Journal of Physiology
M J MayJ D Pearson

Abstract

Work from this and other laboratories has identified a role for protein tyrosine kinases in interleukin-1 alpha (IL-1 alpha)- and tumor necrosis factor-alpha (TNF-alpha)-induced responses in endothelial cells. In this study, we show that activation of human umbilical vein endothelial cells (HUVEC) by IL-1 alpha leads to increased tyrosine phosphorylation of several proteins including one with a molecular mass of approximately 42 kDa. This protein was identified as p42mapk by Western blot analysis. Tyrosine phosphorylation and catalytic activation of p42mapk by IL-1 alpha was transient, reaching maximal levels after 30 min and returning to basal levels by 120-300 min. Activation of p42mapk in HUVEC was also observed in response to TNF-alpha or to the protein kinase C (PKC)-activating phorbol ester phorbol 12-myristate 13-acetate (PMA). Pretreatment of HUVEC with IL-1 alpha or TNF-alpha prevented reactivation of p42mapk by either cytokine but did not affect subsequent activation in response to PMA. Activation of p42mapk by PMA was significantly reduced by the PKC inhibitor Ro-31-8220 and completely inhibited by the protein tyrosine kinase inhibitor genistein. Genistein, but not Ro-31-8220, attenuated IL-1 alpha- and TNF-alpha-ind...Continue Reading

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Citations

Sep 8, 2001·American Journal of Physiology. Cell Physiology·T OshimaJ S Alexander
Jun 21, 2007·Endothelium : Journal of Endothelial Cell Research·Richard DaculsiLaurence Bordenave
Mar 14, 2000·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·A P FlintP A Fisher
Aug 5, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·Y HuM A Gimbrone
Sep 8, 2001·American Journal of Physiology. Cell Physiology·R A HoulistonC P Wheeler-Jones
Jul 29, 2017·Diabetes/metabolism Research and Reviews·Pamela Di TomoGloria Formoso
Nov 22, 2001·Journal of Applied Physiology·A PapapetropoulosJ D Catravas

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