Effect of the steroid receptor antagonist RU486 (mifepristone) on an IFNγ-induced persistent Chlamydophila pneumoniae infection model in epithelial HEp-2 cells
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概要
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We have previously demonstrated that the steroid receptor antagonist mifepristone (RU486) causes growth inhibition of Chlamydophila pneumoniae by binding to and subsequently destroying the bacteria during their normal developmental cycle in epithelial HEp-2 cells. In the present study, we assessed the efficacy of treatment with RU486 against persistent C. pneumoniae infection in interferon (IFN)γ-treated HEp-2 cells. Assessment of bacterial growth modification, the number of infectious progenies, the formation of inclusions, and the expressions of the C. pneumoniae genes 16S rRNA and hsp60 were investigated in cells with or without IFNγ stimulation in the presence of RU486, using an inclusion-forming unit (IFU) assay, fluorescence microscopic analysis, and reverse transcription polymerase chain reaction (RT-PCR), respectively. Our results indicated that RU486 treatment produced growth inhibition and an absence of C. pneumoniae gene expression in normal HEp-2 cells and that this treatment failed to inhibit C. pneumoniae growth in HEp-2 cells stimulated with IFNγ. These results indicate that treatment with RU486 had a limited effect on C. pneumoniae growth only during the active developmental stage of the bacteria, suggesting that the bacterial target molecule of RU486 is not expressed sufficiently during persistent infection in which there is an aberrant developmental cycle. Thus, our findings provide valuable insight into the complicated chlamydial biological processes involved in the recurrent cycling between normal and persistent infections.
- 2012-02-01
著者
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Osaki T
Department Of Infectious Diseases Kyorin University School Of Medicine
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Osaki Takako
Dep. Of Infectious Diseases Div. Of Medical Microbiology Kyorin Univ. School Of Medicine
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Kobayashi Miho
Department Of Legal Medicine Osaka University Medical School
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Yamamoto Yoshimasa
Division Of Applied Biosciences Graduate School Of Agriculture Kyoto University
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Hotta T
Division Of Hematology And Oncology Department Of Medicine Tokai University School Of Medicine
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Yamaguchi Hiroyuki
Department Of Applied Biology Faculty Of Textile Science And Technology Shinshu University
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Yamamoto T
Department Of Microbiology Kyorin University School Of Medicine
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Yamaguchi H
Department Of Internal Medicine National Cancer Center Hospital
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Yamaguchi H
Department Of Emergency And Critical Care Medicine Nippon Medical School
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Yamazaki Tomohiro
Department Of Chemistry School Of Science The University Of Tokyo
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MATSUO Junji
Department of Medical Laboratory Sciences, Faculty of Health Sciences, Hokkaido University
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Yamamoto Yoshimasa
Division Of Microbiology Department Of Infectious Disease School Of Medicine Kyorin University
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Kamiya Shigeru
Kyorin Univ. School Of Medicine Tokyo Jpn
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ISHIDA Kasumi
Department of Medical Laboratory Sciences, Faculty of Health Sciences, Hokkaido University
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MOTOHASHI Kazuki
Department of Medical Laboratory Sciences, Faculty of Health Sciences, Hokkaido University
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OSAKI Takako
Laboratory of Molecular Microbiology, Department of Bioinformatics, Osaka University Graduate School of Medicine
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HANAWA Tomoko
Laboratory of Molecular Microbiology, Department of Bioinformatics, Osaka University Graduate School of Medicine
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KAMIYA Shigeru
Laboratory of Molecular Microbiology, Department of Bioinformatics, Osaka University Graduate School of Medicine
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Ishida Kasumi
Department Of Medical Laboratory Sciences Faculty Of Health Sciences Hokkaido University
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Motohashi Kazuki
Department Of Medical Laboratory Sciences Faculty Of Health Sciences Hokkaido University
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Matsuo Junji
Department Of Medical Laboratory Sciences Faculty Of Health Sciences Hokkaido University
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MATSUO JUNJI
Department of Medical Laboratory Science, Faculty of Health Sciences, Hokkaido University
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Kobayashi Miho
Department of Animal Products Research, National Institute of Livestock and Grassland Science
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