Enhancement of human hepatocyte growth factor production by interleukin-1 alpha and -1 beta and tumor necrosis factor-alpha by fibroblasts in culture.

摘要: Human hepatocyte growth factor (hHGF) was first purified from plasma of patients with fulminant hepatic failure (Gohda, E., Tsubouchi, H., Nakayama, Hirono, S., Sakiyama, O., Takahashi, K., Miyazaki, Hashimoto, and Daikuhara, Y. (1988) J. Clin. Invest. 81, 414-419) is now identified to be the same protein as scatter (Weidner, K. M., Arakaki, N., Hartmann, G., Vandekerckhove, J., Weingart, Rieder, Fonatsch, C., Hishida, T., Y., Birchmeier, W. (1991) Proc. Natl. Acad. Sci. U. S. A. 88, 7001-7005) tumor cytotoxic (Shima, Nakao, Ogaki, F., Tsuda, Murakami, A., Higashio, Biochem. Biophys. Res. Commun. 180, 1151-1158), it known produced by fibroblasts in culture. Here we report that inflammatory cytokines such interleukin-1 (IL-1) necrosis (TNF) stimulate production hHGF human embryonic lung fibroblasts, MRC-5, gingival GF-5. Recombinant IL-1 alpha (rhIL-1 alpha) recombinant TNF-alpha (rhTNF-alpha) increased levels culture supernatants MRC-5 GF-5 cells dose-dependently determined an enzyme-linked immunosorbent assay for hHGF. The half-maximal stimulatory concentrations rhIL-1 rhTNF-alpha were about 1ng/ml 10 units/ml, respectively. beta showed almost effect on stimulation immunoreactive two cell lines. However, rhIL-6 failed show range 2-200 units/ml. interferon-beta -gamma also did not activity. Stimulation observed 6-12 h after addition or lasted at least 48 h, suppressed corresponding antiserum. mRNA a dose-dependent manner Northern blot analysis using cDNA probe. In addition, results nuclear run-off transcription experiments regulated increasing gene expression transcriptional rather than change stability. These observations indicate modulate secretion may play important role tissue repair regeneration.