Effects of transforming growth factor α1, interleukin-1β, tumor necrosis factor α and platelet-derived growth factor on the collagen synthesis and the proliferation of periacinal fibroblastoid cells isolated and cultured from rat pancreatic acini

In vivo studies suggest that pancreatic periacinal fibroblasts participate in the development of pancreatic fibrosis, but regulatory mechanisms of their functions and proliferation have not been clarified. In this study, we examined the effects of humoral factors; transforming growth factor β1 (TGFβ1), interleukin-1β (IL-1β), tumor necrosis factor α (TNFα) and platelet-derived growth factor (PDGF), on the intracellular immunoreactive prolyl hydroxylase (IRPH) production, collagen synthesis and cell proliferation of periacinal fibroblastoid cells (PFC) isolated from rat pancreas. TGFβ1, IL-1β and TNFα induced a dose-dependent increase in IRPH production by PFCs. The most striking increase of intracellular IRPH was observed when PFCs were treated with 1.0 ng/ml of TGFβ1. TGFβ1 also significantly increased collagen synthesis at 1.0 ng/ml. Although, PDGF affected neither IRPH production nor collagen synthesis, it enhanced the cell proliferation of PFCs, dose-dependently. IL-1β and TNFα had no effect and TFβ1 rather inhibit the proliferation of PFCs. These findings suggest that both TGFβ1 and PDGF, synthesized locally from the infiltrated inflammatory cells, play important roles in the development of pancreatic fibrosis by increasing the collagen synthesis and enhancing the proliferation of PFCs, respectively, in vivo.