Effects of interferon-gamma 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-gamma (IFN-gamma) under normal and hypoxic conditions.


METHODS
Prospective experimental study.


METHODS
University medical center.


METHODS
Primary cultures of fibroblasts established from peritoneal and adhesion tissue of the same patients.


METHODS
Hypoxia and IFN-gamma treatment of the primary cultured fibroblasts.


METHODS
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.


RESULTS
Adhesion fibroblasts (ADF) have increased basal levels of type I collagen as compared with normal peritoneal fibroblasts (NF). Interferon-gamma 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-gamma in both NF and ADF. Interferon-gamma can block the stimulating effects of hypoxia on type I collagen expression, supporting the antifibrogenic nature of this cytokine.


CONCLUSIONS
Understanding the mechanism by which IFN-gamma exerts its effect will be important in the utilization of this cytokine as a therapy for postoperative adhesion and tissue fibrosis.
Saed
Ghassan M
GM
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Wayne State University School of Medicine-Detroit Medical Center, Detroit, Michigan, USA. g.saed@wayne.edu
Diamond
Michael P
MP
D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage*; D010100:Oxygen / Q000378:metabolism*; D010537:Peritoneum / Q000187:drug effects / Q000378:metabolism*
D016326:Extracellular Matrix Proteins; D007371:Interferon-gamma; D010100:Oxygen