Modulation of the BCL-2/BAX ratio by interferon-gamma and hypoxia in human peritoneal and adhesion fibroblasts.

摘要

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. DESIGN: Prospective experimental study. SETTING: University medical center. PATIENT(S): Fibroblasts from peritoneum and adhesion tissues of 5 patients. INTERVENTION(S): Hypoxia and IFN-gamma treatments of fibroblasts. MAIN OUTCOME MEASURE(S): 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. RESULT(S): 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. CONCLUSION(S): 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.