Modulation of the BCL-2/BAX ratio by interferon-gamma and hypoxia in human peritoneal and adhesion fibroblasts.
OBJECTIVE
To examine the effect of interferon (IFN)-gamma treatment under normal and hypoxic conditions on the BCL-2/BAX ratio of fibroblasts obtained from normal peritoneal and adhesion tissues of the same patients.


METHODS
Prospective experimental study.


METHODS
University medical center.


METHODS
Fibroblasts from peritoneum and adhesion tissues of 5 patients.


METHODS
Hypoxia and IFN-gamma treatments of fibroblasts.


METHODS
We used the multiplex polymerase chain reaction technique to measure expression of BCL-2 and BAX in normal peritoneal and adhesion fibroblasts exposed to hypoxia (2% O(2)), in the presence or absence of IFN-gamma for different time points and dosages.


RESULTS
At baseline, adhesion fibroblasts manifested decreased basal levels of apoptosis compared with normal fibroblasts. Hypoxia treatment resulted in a time-response decrease in apoptosis in both cell lines. Interferon-gamma treatment resulted in a dose-response increase in apoptosis in both cell lines. Hypoxia had a reduced or no effect on apoptosis in the presence of increasing doses of IFN-gamma in both cell types.


CONCLUSIONS
Interferon-gamma can block the effects of hypoxia on apoptosis, supporting the antifibrogenic nature of this cytokine. This suggests that IFN-gamma would be a good candidate for consideration for intervention in the development of peritoneal adhesions and fibrosis.
Saed
Ghassan M
GM
Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, CS Mott Center for Human Growth and Development, Wayne State University, Detroit, Michigan 48201, USA.
Jiang
Zhongliang
Z
Fletcher
Nicole M
NM
Diamond
Michael P
MP
D017209:Apoptosis / Q000187:drug effects; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism* / Q000494:pharmacology; D010532:Peritoneal Diseases / Q000378:metabolism* / Q000473:pathology; D010537:Peritoneum / Q000378:metabolism* / Q000473:pathology; D011446:Prospective Studies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D000267:Tissue Adhesions; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D007371:Interferon-gamma