Aspirin inhibits Chlamydia pneumoniae-induced nuclear factor-kappa B 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)-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.


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.
Department of Laboratory Medicine, University of Graz, Austria. andreas.tiran@uni-graz.at
Andreas
A
Tiran
Hans-Jürgen
HJ
Gruber
Wolfgang F
WF
Graier
Andreas H
AH
Wagner
Ellen B M
EB
Van Leeuwen
Beate
B
Tiran
D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000494:pharmacology*; D002460:Cell Line; D016993:Chlamydophila pneumoniae / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000382:microbiology* / Q000473:pathology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D014471:Umbilical Veins; D000093242:Interleukin-6 Inhibitors
D001241:Aspirin; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D000093242:Interleukin-6 Inhibitors