INDUCTION OF CELL-PROLIFERATION AND COLLAGEN-SYNTHESIS IN HUMAN SMALL-INTESTINAL LAMINA PROPRIA FIBROBLASTS BY LIPOPOLYSACCHARIDE - POSSIBLE INVOLVEMENT OF NITRIC-OXIDE

Recent studies suggest that tissue specific fibroblasts respond to inf lammatory stimuli leading to the onset of inflammatory disorders. In t he present study, we investigated cell kinetics, collagen synthesis, a nd nitric oxide (NO) level in cultured human small intestinal lamina p ropria fibroblasts (HSILPF, n=45) in response to LPS of enteropathogen ic E.coLi. LPS treatment enhanced the (3)[H] TdR uptake, increased the percentage of 'S' phase cells as early as 4 hrs, and decreased the po pulation doubling time of HSILPF in a dose and time dependent manner. Collagen synthesis in HSILPF was also elevated by LPS. The LPS induced cell proliferation and collagen synthesis were inhibited by polymyxin B (10 mu g/ml), LPS was found to supress the NO production in these c ells, whereas combination of LPS (10 mu g/ml) and IFN gamma (100 U/ml) enhanced NO output and concurrently decreased the cell proliferation and collagen production in HSILPF. Inhibitors of NO, L-N-G-monomethyl L-arginine, and aminoguanidine partially restored cell proliferation a nd collagen synthesis in cells exposed to LPS and IFN gamma. These fin dings suggest that LPS induces increased cell proliferation and collag en synthesis in HSILPF and these could be related to the suppression o f NO production. (C) 1997 Academic Press.