The aim of the study was to evaluate the biological response of human Schwann cells (SC) to tumor necrosis factor α (TNFα) 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 TNFα promoted in SC cultures transient activation of transcription factors NFκB and c-jun in the absence of apoptosis. In addition, TNFα 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 NFκB, as assessed by functional blockage with acetylsalicylic acid. We then extended our study to a human disease in which SC are exposed to TNFα. Increased signals for NFκB, 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 TNFα and that this cytokine exerted no cytotoxic effects either in vivo or in vitro. Rather, TNFα may influence the fate of SC by activating transcriptional pathways and modulating their phenotype.

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

Zanusso G.;Ramarli D.;Turazzi S.;Carner M.;Moretto G.
2000-01-01

Abstract

The aim of the study was to evaluate the biological response of human Schwann cells (SC) to tumor necrosis factor α (TNFα) 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 TNFα promoted in SC cultures transient activation of transcription factors NFκB and c-jun in the absence of apoptosis. In addition, TNFα 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 NFκB, as assessed by functional blockage with acetylsalicylic acid. We then extended our study to a human disease in which SC are exposed to TNFα. Increased signals for NFκB, 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 TNFα and that this cytokine exerted no cytotoxic effects either in vivo or in vitro. Rather, TNFα may influence the fate of SC by activating transcriptional pathways and modulating their phenotype.
C-jun; De-differentiation; NFκB; NGF receptor; Schwann cells; TNFα; Transcription factors;
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/305545
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