Aspirin inhibits Chlamydia pneumoniae-induced NF-κB activation, cyclo-oxygenase-2 expression and prostaglandin E2 synthesis and attenuates chlamydial growth

Abstract

Infection with Chlamydia pneumoniae has been implicated as a potential risk factor for atherosclerosis. This study was designed to investigate the mechanisms of the anti-chlamydial activity of aspirin. A reporter gene assay for NF-κB activity, immunoblot analysis for cyclo-oxygenase (COX)-2 and radioimmunoassay for prostaglandin E2 (PGE2) were performed. Following infection of HEp-2 cells with C. pneumoniae, NF-κB was activated, COX-2 was induced and PGE2 was elevated. Aspirin inhibited NF-κB activation at a concentration of 0.1 mM, partially inhibited COX-2 induction and blocked PGE2 synthesis completely. In addition, high doses of aspirin (1 and 2 mM) inhibited chlamydial growth in HEp-2 cells, decreasing the number and size of inclusion bodies; this effect could be overcome by adding tryptophan to the culture. Indomethacin also blocked the synthesis of PGE2, but had no effect on COX-2 expression or chlamydial growth. These results indicate that aspirin not only has an anti-inflammatory activity through prevention of NF-κB activation but also has anti-chlamydial activity at high doses, possibly through depletion of tryptophan in HEp-2 cells.