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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1075.)
© 2002 American Heart Association, Inc.

Vascular Biology

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

Andreas Tiran; Hans-Jürgen Gruber; Wolfgang F. Graier; Andreas H. Wagner; Ellen B.M. van Leeuwen; Beate Tiran

From the Department of Laboratory Medicine (A.T., H-J.G., B.T) and the Institute of Medical Biochemistry and Medical Molecular Biology (W.F.G.), University of Graz, Graz, Austria; the Department of Cardiovascular Physiology (A.H.W.), University of Goettingen, Goettingen, Germany; and the Department of Haematology (E.B.M.v.L.), University of Groningen, Groningen, the Netherlands.

Correspondence to Andreas Tiran, Department of Laboratory Medicine, University of Graz, Auenbruggerplatz 15, A-8036 Graz, Austria. E-mail andreas.tiran{at}uni-graz.at

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)-B, a transcription factor. The present study was designed to test the effect of aspirin on C pneumoniae–induced NF-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-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-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-B by aspirin also reduced the secretion of interleukin-6 and interleukin-8, indicating efficient inhibition of NF-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-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-B activation, which might account for some of the cardioprotective activity of aspirin.

Key Words: aspirin • transcription factor • Chlamydia pneumoniae • nuclear factor-B

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