| Autor: |
Vervoordeldonk, Margriet J.B.M., Pineda Torra, Inés M., Aarsman, Anton J., van den Bosch, Henk |
| Zdroj: |
FEBS Letters; November 1996, Vol. 397 Issue: 1 p108-112, 5p |
| Abstrakt: |
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 A2(sPLA2) 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 sPLA2activity in rat mesangial cells in a dose‐dependent manner. The IC50value of aspirin for sPLA2inhibition was 6.5 mM. This decrease in sPLA2activity was not due to direct inhibition of enzymatic activity but rather to the fact that aspirin inhibits the expression of IL‐1β‐induced sPLA2protein 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 sPLA2gene transcription, after treatment of the cells with aspirin. The study described in this report indicates that the inhibition of sPLA2expression as induced by pro‐inflammatory cytokines potentially represents an additional mechanism of action for aspirin. |
| Databáze: |
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