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 tumor necrosis factor alpha (TNFalpha) 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 TNFalpha promoted in SC cultures transient activation of transcription factors NFkappaB and c-jun in the absence of apoptosis. In addition, TNFalpha 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 NFkappaB, as assessed by functional blockage with acetylsalicylic acid. We then extended our study to a human disease in which SC are exposed to TNFalpha. Increased signals for NFkappaB, 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 TNFalpha and that this cytokine exerted no cytotoxic effects either in vivo or in vitro. Rather, TNFalpha may influence the fate of SC by activating transcriptional pathways and modulating their phenotype.
Bonetti
B
B
Sezione di Neurologia Cliica, Dipartimento di Scienze Neurologiche e della Visione, Università di Verona, Italy.
Valdo
P
P
Stegagno
C
C
Tanel
R
R
Zanusso
G L
GL
Ramarli
D
D
Fiorini
E
E
Turazzi
S
S
Carner
M
M
Moretto
G
G
D017209:Apoptosis; D001706:Biopsy; D005786:Gene Expression Regulation; D006801:Humans; D020287:In Situ Nick-End Labeling; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000032:analysis; D009442:Neurilemmoma; D010641:Phenotype; D010766:Phosphorylation; D020277:Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / Q000473:pathology / Q000503:physiopathology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000032:analysis; D012583:Schwann Cells / Q000737:chemistry / Q000166:cytology* / Q000201:enzymology*; D012584:Sciatic Nerve / Q000166:cytology; D015398:Signal Transduction / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000201:enzymology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D016328:NF-kappa B; D016755:Proto-Oncogene Proteins c-jun; D017475:Receptors, Nerve Growth Factor; D014409:Tumor Necrosis Factor-alpha; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases