SYNERGISTIC INCREASE IN NERVE GROWTH-FACTOR SECRETION BY CULTURED VASCULAR SMOOTH-MUSCLE CELLS TREATED WITH INJURY-RELATED GROWTH-FACTORS

Vascular smooth muscle (VSM) cells comprise one of the primary targets of the sympathetic nervous system and have been shown to secrete nerv e growth factor (NGF), There is increasing evidence that changes in th e levels of NGF in the adult may underlie certain pathological conditi ons, To investigate the potential role of altered NGF production in va scular disease, VSM cell cultures were treated with injury-related gro wth factors and the culture medium was assayed for NGF using a two-sit e enzyme-linked immunosorbent assay (ELISA), Platelet-derived growth f actor (PDGF), a potent VSM mitogen, caused a dose-dependent increase i n NGF secretion, After 4 hr, PDGF-treated cultures contained 10 times more NGF than control cultures, NGF release remained elevated for 48 h r, but the peak secretion occurred in the first 12 hr after treatment, Transforming growth factor beta (TGF-beta) caused a fivefold increase in NGF at 4 hr when added alone, but synergized with PDGF yielding ap proximately 50 times more NGF than control cultures, TGF-beta and epid ermal growth factor (EGF) also displayed synergism, In contrast, basic fibroblast growth factor (bFGF), which had a modest effect alone, app eared to be additive with TGF-beta. Similarly, interleukin 1-beta (IL- 1 beta), which mediates increased NGF synthesis in sciatic nerve lesio ns (Lindholm et al.: Nature 330:658-659, 1987), showed no synergism wi th TGF-beta. (C) 1997 Wiley-Liss, Inc.