Effects of synthetic serine protease inhibitors on proliferation and collagen synthesis of human pancreatic periacinar fibroblast-like cells

Protease inhibitors are currently used as therapeutic agents for chronic pancreatitis in Japan. We previously reported that human pancreatic periacinar fibroblast-like cells (hPFCs) could be cultured from isolated pancreatic acini, and those are thought to play a crucial role in pancreatic fibrosis correlating with platelet-derived growth factor (PDGF) and transforming growth factor beta1 (TGF-beta1) (Pancreas 1997;14: 373-82. The present study was designed to examine the effects of synthetic serine protease inhibitors (FOY-007 and FOY-305) on proliferation and collagen synthesis of hPFCs under cytokine stimulation. The cell proliferation and collagen synthesis were evaluated using assays of [H-3]-thymidine incorporation and procollagen type I c-terminal peptide (PIP), and [C-14]-proline incorporation to de novo synthesized collagen, respectively. The cell proliferation stimulated by PDGF was inhibited by the application of FOY-007 dose dependently (1-100 muM) and FOY-305 at 100 muM. FOY-007 attenuated the collagen synthesis and PIP production stimulated by TGF-beta1 dose dependently, but FOY-305 inhibited only PIP production. Both protease inhibitors demonstrated no effect on the proliferation and collagen synthesis of hPFCs when they were not stimulated by PDGF or TGF-beta1. Thus, serine protease inhibitors act on hPFCs to diminish the effects of PDGF on proliferation and the effects of TGF-beta1 on collagen synthesis.