TNF-α as an autocrine mediator and its role in the activation of Schwann cells

In the peripheral nervous system (PNS), tumor necrosis factor-alpha (TNF-alpha) derived from activated Schwann cells (SCs) play a critical role as a pleiotropic mediator. In this study, we examined the function of TNF-alpha as an inflammatory mediator in SCs activation. TNF-alpha exhibits its biological effect through two distinct surface receptors, TNF receptor 1 (TNFR1) and TNFR2. We show here that cultured SCs express both TNFR1 and TNFR2, and that activation of these receptors by TNF-alpha promotes expression of TNF-alpha. Meanwhile, TNF-alpha also increased the production of other inflammatory mediators. Furthermore, TNF-alpha is involved in the induction of apoptosis through binding to TNFR in SCs. The activation of SCs by lipopolysaccharide (LPS) is partially mediated by SCs-derived TNF-alpha. These findings suggest the existence of a positive feedback loop in the activation of SC via TNF-alpha. This loop may be involved in the prolonged activation of SCs. Acute or chronic stimulation of TNF-alpha by SC at sites of PNS inflammation may be critical in determining whether TNF-alpha has activational, inflammatory, or cytotoxic effects on these cells.