Aspirin inhibits expression of the interleukin-1beta-inducible group II phospholipase A2

FEBS Letters
M VervoordeldonkH van den Bosch

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) clearly inhibit the synthesis and release of prostaglandins. However, these actions are not sufficient to explain all the anti-inflammatory effects of these drugs. Recently, it has been shown that aspirin and sodium salicylate inhibit the activation of the transcription factor NF-kappaB. Group II phospholipase A2 (sPLA2) is expressed in rat glomerular mesangial cells upon exposure to the inflammatory cytokine interleukin-1beta (IL-1beta) and this induction is attenuated by the NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC). We now report that aspirin inhibits the IL-1beta-induced sPLA2 activity in rat mesangial cells in a dose-dependent manner. The IC50 value of aspirin for sPLA2 inhibition was 6.5 mM. This decrease in sPLA2 activity was not due to direct inhibition of enzymatic activity but rather to the fact that aspirin inhibits the expression of IL-1beta-induced sPLA2 protein and mRNA. Furthermore, by electrophoretic mobility shift analysis we demonstrate reduced DNA binding of the nuclear factor kappaB, an essential component of the IL-1beta-dependent upregulation of sPLA2 gene transcription, after treatment of the cells with aspirin. The study described in this report ...Continue Reading

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Citations

Apr 13, 2000·Biochimica Et Biophysica Acta·H A van der HelmH van den Bosch
Jan 25, 2002·Annual Review of Pharmacology and Toxicology·Camilla I Svensson, Tony L Yaksh
Nov 24, 1998·Journal of Clinical Pharmacology·J I Lee, G J Burckart
Jul 25, 2000·Biochemical and Biophysical Research Communications·B HinzK Brune
Jan 1, 2012·ISRN Inflammation·M S AhmedQing H Meng
Jun 19, 2018·Scandinavian Journal of Pain·Yang YangJian-Qiang Yu
May 25, 2013·World Journal of Gastroenterology : WJG·Ibrahim AkyaziMukaddes Ozcan
Dec 10, 2003·Expert Opinion on Emerging Drugs·Christian Waeber
Oct 19, 2011·Archives of Insect Biochemistry and Physiology·Koigoora SrikanthYonggyun Kim
Jul 21, 1999·Kidney International. Supplement·Z A MassyW F Keane

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