Chlamydia pneumoniae Growth Inhibition in Cells by Steroid Receptor Antagonist RU486
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Since steroids are powerful anti-inflammatory agents and increase susceptibility to a variety of infections, including Chlamydia (Chlamydophila) pneumoniae respiratory infection, the effect of the steroid receptor antagonist RU486 mifepristone on C. pneumoniae growth in epithelial HEp-2 cells was examined. Treatment of HEp-2 cells with RU486 significantly inhibited growth of C. pneumoniae in a dose-dependent manner. Electron microscopic studies also revealed that the treatment of infected cells with RU486 resulted in a marked destruction of infecting organisms. The addition of the host cell protein synthesis inhibitor cycloheximide to the infected cells did not alter the C. pneumoniae growth inhibition by RU486. Pre-treatment of C. pneumoniae organisms with RU486 before addition to culture also did not result in any modulation of bacterial growth in the cells. However, the binding of RU486 to C. pneumoniae organisms in cells at 24 h after infection was demonstrated by immune electron microscopy with anti-RU486 antibody. Incubation of cells with anti-RU486 antibody completely diminished the C. pneumoniae growth inhibition by RU486. These results indicate that RU486 may directly bind to bacteria within cells and causes a destruction of C. pneumoniae. This novel regulation of C. pneumoniae growth in cells by RU486 might provide a new approach for understanding complicated aspect of C. pneumoniae infection.
Yamaguchi H, Kamiya S, Uruma T, Osaki T, Taguchi H, Hanawa T, Fukuda M, Kawakami H, Goto H, Friedman H, Yamamoto Y.
Division of Microbiology, Department of Infectious Disease, Department of 1 Internal Medicine, Laboratory of Electron Microscopy, and Department of Anatomy, Kyorin University, School of Medicine, Tokyo 181-8611, Japan; Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, Tampa, Florida 33612; Division of Molecular Microbiology, Department of Basic Laboratory Sciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan; Department of Laboratory Sciences, College of Medical Technology, Hokkaido University, Nishi-5 Kita-12 Jo, Kita-ku, Sapporo, Hokkaido 060-0812, Japan.
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