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

Hiroshi Yoneda^1,2, Koshiro Miura^1,4, Hiroshi Matsushima^1,3, Kazuro Sugi⁴, Tomoyuki Murakami⁴, Kazunobu Ouchi^5,, Katsuhiro Yamashita^2,, Haruhide Itoh^2,, Teruko Nakazawa¹, Michiyasu Suzuki² and Mutsunori Shirai¹

^1–3Departments of Microbiology¹, Neurosurgery² and Pediatrics³, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan ⁴Department of Clinical Research, National Sanyo Hospital, Ube, Yamaguchi, 755-0241, Japan ⁵Saiseikai General Hospital, Shimonoseki, Yamaguchi, 751-0823, Japan

Correspondence Mutsunori Shirai mshirai{at}po.cc.yamaguchi-u.ac.jp

Received June 11, 2002
Accepted December 11, 2002

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-B 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-B was activated, COX-2 was induced and PGE₂ was elevated. Aspirin inhibited NF-B 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-B activation but also has anti-chlamydial activity at high doses, possibly through depletion of tryptophan in HEp-2 cells.

Present address: Yamaguchi Rosai Hospital, Onoda, Yamaguchi, 756-0803, Japan.

Present address: Neurosurgery, Shimonoseki National Hospital, Shimonoseki, Yamaguchi, 751-0823, Japan.

Abbreviations: COX, cyclo-oxygenase; PGE₂, prostaglandin E₂.

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