Effects of interferon-γ reverse hypoxia-stimulated extracellular matrix expression in human peritoneal and adhesion fibroblasts

Objective: To determine the response of adhesion and normal peritoneal fibroblasts to interferon-γ (IFN-γ) under normal and hypoxic conditions. Design: Prospective experimental study. Setting: University medical center. Patient(s): Primary cultures of fibroblasts established from peritoneal and adhesion tissue of the same patients. Intervention(s): Hypoxia and IFN-γ treatment of the primary cultured fibroblasts. Main Outcome Measure(s): Primary cultures of fibroblasts were established from peritoneal and adhesion tissues of the same patients (n = 5). The expression of extracellular matrix components (type I collagen and fibronectin) in adhesion and peritoneal fibroblasts under normal (20% O₂) and hypoxic (2% O₂) conditions was evaluated by multiplex reverse-transcription polymerase chain reaction analysis. Result(s): Adhesion fibroblasts (ADF) have increased basal levels of type I collagen as compared with normal peritoneal fibroblasts (NF). Interferon-γ treatment resulted in a dose-response decrease in type I collagen and fibronectin mRNA levels in both ADF and NF. Hypoxia treatment resulted in a time-response increase in type I collagen and fibronectin mRNA levels in NF and ADF. Hypoxia had no effect on type I collagen and fibronectin mRNA levels in the presence of increasing dose of IFN-γ in both NF and ADF. Interferon-γ can block the stimulating effects of hypoxia on type I collagen expression, supporting the antifibrogenic nature of this cytokine. Conclusion(s): Understanding the mechanism by which IFN-γ exerts its effect will be important in the utilization of this cytokine as a therapy for postoperative adhesion and tissue fibrosis.