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Aspirin inhibits expression of the interleukin‐1β‐inducible group II phospholipase A 2
Author(s) -
Vervoordeldonk Margriet J.B.M.,
Pineda Torra Inés M.,
Aarsman Anton J.,
van den Bosch Henk
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(96)01148-9
Subject(s) - pyrrolidine dithiocarbamate , aspirin , sodium salicylate , phospholipase a2 , phospholipase a , chemistry , cytokine , pharmacology , electrophoretic mobility shift assay , phospholipase , cyclooxygenase , interleukin , transcription factor , nfkb1 , mechanism of action , enzyme , nf κb , biochemistry , biology , immunology , signal transduction , gene , in vitro
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‐κB. Group II phospholipase A 2 (sPLA 2 ) is expressed in rat glomerular mesangial cells upon exposure to the inflammatory cytokine interleukin‐1β (IL‐1β) and this induction is attenuated by the NF‐κB inhibitor pyrrolidine dithiocarbamate (PDTC). We now report that aspirin inhibits the IL‐1β‐induced sPLA 2 activity in rat mesangial cells in a dose‐dependent manner. The IC 50 value of aspirin for sPLA 2 inhibition was 6.5 mM. This decrease in sPLA 2 activity was not due to direct inhibition of enzymatic activity but rather to the fact that aspirin inhibits the expression of IL‐1β‐induced sPLA 2 protein and mRNA. Furthermore, by electrophoretic mobility shift analysis we demonstrate reduced DNA binding of the nuclear factor κB, an essential component of the IL‐1β‐dependent upregulation of sPLA 2 gene transcription, after treatment of the cells with aspirin. The study described in this report indicates that the inhibition of sPLA 2 expression as induced by pro‐inflammatory cytokines potentially represents an additional mechanism of action for aspirin.