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

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)-kB, a transcription factor. The present study was designed to test the effect of aspirin on C pneumoniae–induced NF-kB activation, interleukin expression, and bacterial development in cultured human endothelial cells. Methods and Results—Aspirin, its metabolite salicylic acid, and 2 other unrelated NF-kB 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-kB was confirmed by electrophoretic mobility shift assay and by transfection experiments with appropriate decoy oligodeoxynucleotides. Attenuation of the C pneumoniae–induced activation of NF-kB by aspirin also reduced the secretion of interleukin-6 and interleukin-8, indicating efficient inhibition of NF-kB 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-kB–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-kB activation, which might account for some of the cardioprotective activity of aspirin. (Arterioscler Thromb Vasc Biol. 2002;22:●●●-●●●.)