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

Autor: Chiara Stegagno, Raffaella Tanel, Gianluigi Zanusso, Giuseppe Moretto, Dunia Ramarli, Emma Fiorini, Marco Carner, Paola Valdo, Bruno Bonetti, Sergio Turazzi
Jazyk: angličtina
Rok vydání: 2000
Předmět:
medicine.medical_specialty
Programmed cell death
Proto-Oncogene Proteins c-jun
Biopsy
medicine.medical_treatment
Schwann cell
De-differentiation
Apoptosis
Inflammation
Receptors
Nerve Growth Factor
NGF receptor
Biology
Pathology and Forensic Medicine
C-jun
NFκB
Schwann cells
TNFα
Transcription factors
Cellular and Molecular Neuroscience
Internal medicine
In Situ Nick-End Labeling
Tumor Cells
Cultured
medicine
Humans
Phosphorylation
Receptor
Tumor Necrosis Factor-alpha
JNK Mitogen-Activated Protein Kinases
NF-kappa B
General Medicine
Sciatic Nerve
Phenotype
medicine.anatomical_structure
Cytokine
Endocrinology
Gene Expression Regulation
Polyradiculoneuropathy
Chronic Inflammatory Demyelinating
Neurology
Cancer research
Tumor necrosis factor alpha
Neurology (clinical)
Mitogen-Activated Protein Kinases
medicine.symptom
Signal transduction
Neurilemmoma
Signal Transduction
Zdroj: Scopus-Elsevier
Popis: 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.
Databáze: OpenAIRE
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