Aspirin Inhibits Chlamydia pneumoniae–Induced Nuclear Factor-&kgr;B Activation, Cytokine Expression, and Bacterial Development in Human Endothelial Cells

Abstract

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)-&kgr;B, a transcription factor. The present study was designed to test the effect of aspirin on C pneumoniae–induced NF-&kgr;B activation, interleukin expression, and bacterial development in cultured human endothelial cells. Methods and Results—Aspirin, its metabolite salicylic acid, and 2 other unrelated NF-&kgr;B 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-&kgr;B was confirmed by electrophoretic mobility shift assay and by transfection experiments with appropriate decoy oligodeoxynucleotides. Attenuation of the C pneumoniae–induced activation of NF-&kgr;B by aspirin also reduced the secretion of interleukin-6 and interleukin-8, indicating efficient inhibition of NF-&kgr;B 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-&kgr;B–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-&kgr;B activation, which might account for some of the cardioprotective activity of aspirin.