Document Detail


Effect of the steroid receptor antagonist RU486 (mifepristone) on an IFNγ-induced persistent Chlamydophila pneumoniae infection model in epithelial HEp-2 cells.
MedLine Citation:
PMID:  21744047     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Kasumi Ishida; Tomohiro Yamazaki; Kazuki Motohashi; Miho Kobayashi; Junji Matsuo; Takako Osaki; Tomoko Hanawa; Shigeru Kamiya; Yoshimasa Yamamoto; Hiroyuki Yamaguchi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-07-09
Journal Detail:
Title:  Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy     Volume:  18     ISSN:  1437-7780     ISO Abbreviation:  J. Infect. Chemother.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-14     Completed Date:  2012-09-04     Revised Date:  2013-03-28    
Medline Journal Info:
Nlm Unique ID:  9608375     Medline TA:  J Infect Chemother     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  22-9     Citation Subset:  IM    
Affiliation:
Department of Medical Laboratory Sciences, Faculty of Health Sciences, Hokkaido University, Nishi-5 Kita-12 Jo, Kita-ku, Sapporo, Hokkaido, 060-0812, Japan.
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MeSH Terms
Descriptor/Qualifier:
Anti-Bacterial Agents / pharmacology
Cell Line
Cell Survival / drug effects
Chlamydophila Infections / drug therapy*,  microbiology
Chlamydophila pneumoniae / drug effects*
Epithelial Cells / drug effects,  microbiology
Hormone Antagonists / pharmacology
Host-Pathogen Interactions / drug effects
Humans
Interferon-gamma / pharmacology*
Microscopy, Fluorescence
Mifepristone / pharmacology*
Chemical
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Hormone Antagonists; 82115-62-6/Interferon-gamma; 84371-65-3/Mifepristone
Comments/Corrections
Erratum In:
J Infect Chemother. 2013 Feb;19(1):184-5

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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