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 [3H]-thymidine incorporation and procollagen type I c-terminal peptide (PIP), and [14C]-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 microM) and FOY-305 at 100 microM. 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.
Nakamura
F
F
Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan. fumi@pop.biwako.ne.jp
Shintani
Y
Y
Saotome
T
T
Fujiyama
Y
Y
Bamba
T
T
D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D004952:Esters; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D016670:Gabexate / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D010179:Pancreas / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011392:Proline / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014316:Tritium
D004952:Esters; D006146:Guanidines; D010982:Platelet-Derived Growth Factor; D015842:Serine Proteinase Inhibitors; D016212:Transforming Growth Factor beta; C034532:camostat; D014316:Tritium; D016670:Gabexate; D003094:Collagen; D011392:Proline; D013936:Thymidine