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

Objective: To examine the effect of interferon (IFN)-γ 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-γ 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% O₂), in the presence or absence of IFN-γ 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-γ 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-γ in both cell types. Conclusion(s): Interferon-γ can block the effects of hypoxia on apoptosis, supporting the antifibrogenic nature of this cytokine. This suggests that IFN-γ would be a good candidate for consideration for intervention in the development of peritoneal adhesions and fibrosis.