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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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Title: Effect of the steroid receptor antagonist RU486 (mifepristone) on an IFNγ-induced persistent Chlamydophila pneumoniae infection model in epithelial HEp-2 cells
Authors: Ishida, Kasumi Browse this author
Yamazaki, Tomohiro Browse this author
Motohashi, Kazuki Browse this author
Kobayashi, Miho Browse this author
Matsuo, Junji Browse this author →KAKEN DB
Osaki, Takako Browse this author
Hanawa, Tomoko Browse this author
Kamiya, Shigeru Browse this author
Yamamoto, Yoshimasa Browse this author
Yamaguchi, Hiroyuki Browse this author →KAKEN DB
Keywords: Chlamydophila pneumoniae
Steroid receptor antagonist
Persistent infection
Issue Date: Feb-2012
Publisher: 日本化学療法学会・日本感染症学会
Journal Title: Journal of Infection and Chemotherapy
Volume: 18
Issue: 1
Start Page: 22
End Page: 29
Publisher DOI: 10.1007/s10156-011-0274-6
PMID: 21744047
Abstract: 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.
Rights: The original publication is available at
Type: article (author version)
Appears in Collections:保健科学院・保健科学研究院 (Graduate School of Health Sciences / Faculty of Health Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 山口 博之

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