INDUCTION OF LIF-MESSENGER-RNA BY TGF-BETA-1 IN SCHWANN-CELLS

Schwann cell is a cell type that forms myelin sheath and provides trop hic supports for neuronal cells by producing neurotrophic factors such as neurotrophins and neurokines in both normal and traumatic situatio ns. It was recently reported that after lesion of sciatic nerve, mRNA for cholinergic differentiation factor (CDF)/leukemia inhibitory facto r (LIF) is induced in nonneuronal cells in the nerve. However, the sou rce of LIF-mRNA and the mechanism of LIF-mRNA regulation have remained largely unknown. In the present study, we searched for factors regula ting the LIF-mRNA expression in cultured Schwann cells isolated from n ewborn rat sciatic nerve. Among various growth factors and cytokines t ested, TGF beta-1 exerted the most prominent effect on the induction o f LIF-mRNA in the cultured Schwann cells. The effect of TGF-beta 1 on the increase of LIF-mRNA levels was suppressed by either staurosporine or H-7 suggesting the role of PKC or PKC-like protein kinase activity in the induction of LIF-mRNA. The induction of LIF mRNA by TGF-beta 1 was suppressed in the co-culture of the Schwann cells with embryonic rat DRG neurons. The addition of ascorbic acid, which is known to prom ote myelination in this co-culture system, further suppressed the TGF- beta 1 induction of LIF-mRNA. These results suggest that Schwann cells respond to TGF-beta 1 in a lesion situation to produce LIF, which sup ports neuronal survival and regeneration. The re-establishment of neur on-Schwann cell interaction would in rum suppress the LIF production t o terminate its action during the lesion situation. (C) 1997 Elsevier Science B.V.