Lactoferrin promotes nerve growth factor synthesis/secretion in mouse fibroblast L-M cells

Fibroblast cells are known to have an ability to synthesize and secrete nerve growth factor (NGF). To investigate the mechanism of action of the iron-binding protein, lactoferrin (Lf), on cultured animal cells, the effect of bovine Lf (bLf) on NGF synthesis/secretion in mouse fibroblast cells was examined. Both apo- and holo-bLf induced an increase in NGF content in the cell-conditioned medium(CM) of mouse L-M cells, a line derived from L929 fibroblast cells, with similar effectiveness. The increase in NGF content in the CM of L-M cells cultured with bLf was not dependent on the induction of increase in cell numbers, but was due to induction of de novo synthesis of NGF in individual cells by bLf. Human Lf(hLf) also increased NGF content. However, apo- and holo-bovine transferrin (bTf) failed to stimulate the NGF synthesis. The time-dependent induction of NGF in L-M cells by bLf was different from that induced by basic fibroblast growth factor (bFGF) and bLf showed an additive effect with bFGF. These results suggest that the induction of NGF synthesis depends on a mechanism different from iron transport or bFGF.