Tumor necrosis factor alpha and human Schwann cells: Signalling and phenotype modulation without cell death

The aim of the study was to evaluate the biological response of human Schwann cells (SC) to turner necrosis factor alpha (TNF alpha) in vitro and to the inflammatory milieu of chronic inflammatory demyelinating polyradiculoneuritis (CIDP). By immunocytochemical and functional assays, we found that SC expressed TNF receptors and that TNF alpha promoted in SC cultures transient activation of transcription factors NF kappa B and c-jun in the absence of apoptosis. In addition, TNF alpha significantly increased the proportion of non-myelin-forming SC expressing the p75 nerve growth factor receptor. Such phenotypic effect was dose-dependent and partially mediated by NF kappa B, as assessed by functional blockage with acetylsalicylic acid. We then extended our study to a human disease in which SC are exposed to TNF alpha. Increased signals for NF kappa B, but not c-jun, molecules were observed by immunohistochemistry on SC nuclei in nerve biopsies from patients with CIDP, as compared with controls. Irrespective of the presence of nerve inflammation, SC showed no evidence of apoptosis. Taken together, our results suggested that SC are potential targets of TNF alpha and that this cytokine exerted no cytotoxic effects either in vivo or in vitro. Rather, TNF alpha may influence the fate of SC by activating transcriptional pathways and modulating their phenotype.