Aspirin inhibits Chlamydia pneumoniae-induced NF-kappa B activation, cyclo-oxygenase-2 expression and prostaglandin E2 synthesis and attenuates chlamydial growth.
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-kappa B activity, immunoblot analysis for cyclo-oxygenase (COX)-2 and radioimmunoassay for prostaglandin E(2) (PGE(2)) were performed. Following infection of HEp-2 cells with C. pneumoniae, NF-kappa B was activated, COX-2 was induced and PGE(2) was elevated. Aspirin inhibited NF-kappa B activation at a concentration of 0.1 mM, partially inhibited COX-2 induction and blocked PGE(2) 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 PGE(2), 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-kappa B activation but also has anti-chlamydial activity at high doses, possibly through depletion of tryptophan in HEp-2 cells.
Departments 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.
Hiroshi
H
Yoneda
Departments 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.
Koshiro
K
Miura
Departments 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.
Hiroshi
H
Matsushima
Departments 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.
Kazuro
K
Sugi
Departments 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.
Tomoyuki
T
Murakami
Departments 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.
Kazunobu
K
Ouchi
Departments 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.
Katsuhiro
K
Yamashita
Departments 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.
Haruhide
H
Itoh
Departments 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.
Teruko
T
Nakazawa
Departments 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.
Michiyasu
M
Suzuki
Departments 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.
Mutsunori
M
Shirai
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D016993:Chlamydophila pneumoniae / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D008565:Membrane Proteins; D016328:NF-kappa B / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D014364:Tryptophan / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D016328:NF-kappa B; D009569:Nitric Oxide; D014364:Tryptophan; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D001241:Aspirin; D007213:Indomethacin