Effect of the steroid receptor antagonist RU486 (mifepristone) on an IFNγ-induced persistent Chlamydophila pneumoniae infection model in epithelial HEp-2 cells.
نویسندگان
چکیده
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.
منابع مشابه
Chlamydia pneumoniae growth inhibition in cells by the steroid receptor antagonist RU486 (mifepristone).
Since steroids are powerful anti-inflammatory agents and increase susceptibility to a variety of infections, including Chlamydia (Chlamydophila) pneumoniae respiratory tract infections, 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 the growth of C. pne...
متن کاملChlamydia pneumoniae Growth Inhibition in Cells by Steroid Receptor Antagonist RU486 Mifepristone
متن کامل
O-31: Mifepristone Acts as Progesterone Antagonistof Non-Genomic Responses but InhibitsPhytohemagglutinin Induced Proliferationin Human T Cells
Background: Progesterone is an endogenous immunomodulator that suppresses T cell activation during pregnancy. The stimulation of membrane progesterone receptors (mPRs) would seem to be the cause of rapid non-genomic responses in human peripheral T cells, such as an elevation of intracellular calcium ([Ca2+] i) and decreased intracellular pH (pHi). Mifepristoneimmune cells compared with progeste...
متن کاملA Chlamydia pneumoniae infection model using established human lymphocyte cell lines.
Since current studies indicate possible infection of human lymphocytes with Chlamydia (Chlamydophila) pneumoniae, establishment of an in vitro C. pneumoniae infection model using lymphocyte cell lines was demonstrated. Human lymphoid cell lines (Molt 4 [T-cell] and P3HR1 [B-cell]) were utilized for this purpose besides human monocyte cell line (THP-1) and human epithelial cell line (HEp-2), as ...
متن کاملInvolvement of nicotinic acetylcholine receptors in controlling Chlamydia pneumoniae growth in epithelial HEp-2 cells.
Nicotinic acetylcholine receptors (nAChRs) play an essential role in neurotransmission. Recent studies have indicated that nAChRs may be involved in the regulation of some bacterial infections through immunological mechanisms in macrophages. However, the regulation of infection with Chlamydia pneumoniae, which is a ubiquitous pneumonia-causing bacterium, by an nAChR-mediated mechanism is still ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy
دوره 18 1 شماره
صفحات -
تاریخ انتشار 2012