PCBs enhance collagen I expression from human peritoneal fibroblasts

Objective: To test the effect of four polychlorinated biphenyl congeners (PCB-77, PCB-105, PCB 153, and PCB 180) on expression of three adhesion markers (transforming growth factor [TGF] β1, vascular endothelial growth factor [VEGF], and type I collagen) in normal human peritoneal and adhesion fibroblasts. Design: Cell culture study. Settings: University research laboratory. Patient(s): Primary cultures of normal peritoneal and adhesion fibroblasts were established from three patients. Intervention(s): Fibroblasts were treated with PCB-77, PCB-105, PCB-153, or PCB-180 at 20 ppm for 24 hours. Total RNA was extracted from each treatment and subjected to real-time reverse transcriptase polymerase chain reaction (RT-PCR). Main Outcome and Measure(s): The mRNA levels of type I collagen, VEGF, and TGF-β1. Result(s): Normal human peritoneal fibroblasts expressed type I collagen, VEGF, and TGF-β1. Exposure of normal human fibroblasts to PCB-77, PCB-105, PCB-153, or PCB-180 did not affect mRNA levels of β-actin, the housekeeping gene used to normalized RNA levels for the real-time RT-PCR, nor did it affect cell viability as assessed by trypan blue exclusion. The PCB treatments, compared with control, resulted in no significant change for TGF-β1 or VEGF mRNA levels in normal peritoneal and adhesion fibroblasts. In marked contrast, type I collagen mRNA levels were markedly increased in response to the brief 24 hours' exposure to each PCB treatment in both cell types. Conclusion(s): The finding that PCB-77, PCB-105, PCB-153, and PCB-180 increased the expression of type I collagen in human normal peritoneal and adhesion fibroblasts is the first demonstration of involvement of organochlorines in the pathogenesis of tissue fibrosis. This may implicate organochlorine exposure as an etiologic factor in a wide variety of previously unlinked human ailments characterized by fibrosis.