title: Effect of the steroid receptor antagonist RU486 (mifepristone) on an IFNγ-induced persistent Chlamydophila pneumoniae infection model in epithelial HEp-2 cells.
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.
authors: Department of Medical Laboratory Sciences, Faculty of Health Sciences, Hokkaido University, Nishi-5 Kita-12 Jo, Kita-ku, Sapporo, Hokkaido, 060-0812, Japan.
authors: Kasumi
authors: K
authors: Ishida
authors: Tomohiro
authors: T
authors: Yamazaki
authors: Kazuki
authors: K
authors: Motohashi
authors: Miho
authors: M
authors: Kobayashi
authors: Junji
authors: J
authors: Matsuo
authors: Takako
authors: T
authors: Osaki
authors: Tomoko
authors: T
authors: Hanawa
authors: Shigeru
authors: S
authors: Kamiya
authors: Yoshimasa
authors: Y
authors: Yamamoto
authors: Hiroyuki
authors: H
authors: Yamaguchi
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D023521:Chlamydophila Infections / Q000188:drug therapy* / Q000382:microbiology; D016993:Chlamydophila pneumoniae / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects / Q000382:microbiology; D006727:Hormone Antagonists / Q000494:pharmacology; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D015735:Mifepristone / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D006727:Hormone Antagonists; D015735:Mifepristone; D007371:Interferon-gamma