Aspirin inhibits Chlamydia pneumoniae-induced nuclear factor-kappa B activation, cytokine expression, and bacterial development in human endothelial cells.
| Autor: | Tiran A; Department of Laboratory Medicine, University of Graz, Austria. andreas.tiran@uni-graz.at, Gruber HJ, Graier WF, Wagner AH, Van Leeuwen EB, Tiran B |
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| Jazyk: | angličtina |
| Zdroj: | Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2002 Jul 01; Vol. 22 (7), pp. 1075-80. |
| DOI: | 10.1161/01.atv.0000022695.22369.be |
| Abstrakt: | Objective: Chlamydia pneumoniae has been associated with atherosclerosis. Infection of vascular endothelial cells with C pneumoniae increases the expression of proatherogenic cytokines mediated by nuclear factor (NF)-kappaB, a transcription factor. The present study was designed to test the effect of aspirin on C pneumoniae-induced NF-kappaB activation, interleukin expression, and bacterial development in cultured human endothelial cells. Methods and Results: Aspirin, its metabolite salicylic acid, and 2 other unrelated NF-kappaB inhibitors showed a strong concentration-dependent inhibitory effect on chlamydial growth, indicated by the reduction of bacterial inclusions and the titer of infectious progeny. Involvement of the transcription factor NF-kappaB was confirmed by electrophoretic mobility shift assay and by transfection experiments with appropriate decoy oligodeoxynucleotides. Attenuation of the C pneumoniae-induced activation of NF-kappaB by aspirin also reduced the secretion of interleukin-6 and interleukin-8, indicating efficient inhibition of NF-kappaB gene expression. Reduction of chlamydial growth was not caused by apoptosis of the host cell, as determined by monitoring characteristic chromatin condensation. Conclusions: These data provide evidence that NF-kappaB-mediated gene activation represents a crucial step in the developmental cycle of C pneumoniae. Aspirin exerts an anti-chlamydial effect that is due to the inhibition of C pneumoniae-induced NF-kappaB activation, which might account for some of the cardioprotective activity of aspirin. |
| Databáze: | MEDLINE |
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