PMID- 1655776 OWN - NLM STAT- MEDLINE DCOM- 19911114 LR - 20210210 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 266 IP - 29 DP - 1991 Oct 15 TI - Endogenous basic fibroblast growth factor-dependent induction of collagenase and interleukin-6 in tumor necrosis factor-treated human microvascular endothelial cells. PG - 19162-5 AB - Tumor necrosis factor-alpha (TNF-alpha) has been shown to enhance the synthesis of interleukin-6 (IL-6) and collagenase in human omental microvascular endothelial (HOME) cell (Mawatari, M., Kohno, K., Mizoguchi, H., Matsuda, T., Asoh, K., Van Damme, J. V., Welgus, H. G., and Kuwano, M. (1989) J. Immunol. 143, 1619-1627). In the present study, we have examined whether the TNF-alpha-induced synthesis of IL-6 or collagenase in HOME cells is mediated by an inducible growth factor. Among several growth factors examined, we found that the expression of basic fibroblast growth factor (bFGF) mRNA was the one most prominently enhanced when HOME cells were treated with TNF-alpha. The increase of bFGF mRNA by TNF-alpha in HOME cells was observed in both a dose- and time-dependent manner when assayed by Northern blot analysis. The induction of bFGF mRNA was observed by 3 h after incubation with TNF-alpha, and the maximal increase of 5-fold was obtained after 12 h of incubation with 100 units/ml TNF-alpha. Western blot analysis confirmed the enhanced synthesis of bFGF by TNF-alpha. Metabolic labeling and immunoprecipitation assays of bFGF showed that exposure to TNF-alpha enhanced secretion of bFGF into culture medium and also that TNF-alpha stimulated the production of bFGF molecules with molecular masses of 18, 21, and 22.5 kDa in HOME cells. TNF-alpha induced the expression of collagenase mRNA and IL-6 mRNA in HOME cells as well, and the coadministration of neutralizing anti-bFGF antibody almost completely blocked the effects of TNF-alpha. The treatment of HOME cells with exogenous bFGF significantly stimulated the expression of collagenase mRNA and IL-6 mRNA in HOME cells. Therefore, the biological effects of TNF-alpha on HOME cells may be mediated, at least in part, by TNF-alpha-induced bFGF. FAU - Okamura, K AU - Okamura K AD - Department of Biochemistry, Oita Medical School, Japan. FAU - Sato, Y AU - Sato Y FAU - Matsuda, T AU - Matsuda T FAU - Hamanaka, R AU - Hamanaka R FAU - Ono, M AU - Ono M FAU - Kohno, K AU - Kohno K FAU - Kuwano, M AU - Kuwano M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Interleukin-6) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - 103107-01-3 (Fibroblast Growth Factor 2) RN - EC 3.4.24.3 (Microbial Collagenase) SB - IM MH - Blotting, Northern MH - Blotting, Western MH - Cells, Cultured MH - Endothelium, Vascular/cytology/drug effects/*metabolism MH - Enzyme Induction MH - Fibroblast Growth Factor 2/*metabolism MH - Gene Expression MH - Humans MH - Interleukin-6/*biosynthesis/genetics MH - Microbial Collagenase/*biosynthesis/genetics MH - Precipitin Tests MH - RNA, Messenger/biosynthesis MH - Tumor Necrosis Factor-alpha/*pharmacology EDAT- 1991/10/15 00:00 MHDA- 1991/10/15 00:01 CRDT- 1991/10/15 00:00 PHST- 1991/10/15 00:00 [pubmed] PHST- 1991/10/15 00:01 [medline] PHST- 1991/10/15 00:00 [entrez] AID - S0021-9258(18)54976-0 [pii] PST - ppublish SO - J Biol Chem. 1991 Oct 15;266(29):19162-5.