Characterization of signaling pathways leading to Fas expression induced by TNF-alpha: pivotal role of NF-kappaB

Alessio D'Alessio, D Starace, A Riccioli, C Giampietri, S Petrungaro, Roberta Galli, A Filippini, E Ziparo, P De Cesaris

Risultato della ricerca: Contributo in rivistaArticolo in rivista

27 Citazioni (Scopus)

Abstract

TNF-alpha is known to induce a strong up-regulation of Fas expression in mouse Sertoli cell cultures, leading to their apoptosis triggered by effector FasL-bearing cells. These data suggest that increased Fas expression on the cell surface might be a key event in the pathogenesis of autoimmune orchitis, by inducing a leakage of the blood-tubular barrier as a consequence of Sertoli cell apoptosis. In the present paper, we have investigated the signal transduction mechanisms involved in the regulation of Fas expression induced by TNF-alpha in mouse Sertoli cells. We studied the role of the transcription factor NF-kappaB and of MAPKs in regulating Fas expression. By using Sertoli cells transfected with a NF-kappaB Luc reporter gene, we proved that TNF-alpha activates the IkappaB/NF-kappaB system. Moreover, the use of the proteasome inhibitor lactacystin led us to demonstrate that NF-kappaB is required for TNF-alpha mediated Fas expression. By using specific inhibitors for each MAPK, we confirmed the pivotal role of the IkappaB/NF-kappaB system by demonstrating that ERKs, p38, and JNK are not involved in Fas up-regulation by TNF-alpha. The comprehension of these pathways could be relevant to the knowledge of the pathogenesis of autoimmune disorders in immune privileged districts of the body.
Lingua originaleEnglish
pagine (da-a)473-475
Numero di pagine3
RivistaFASEB JOURNAL
Volume19
DOI
Stato di pubblicazionePubblicato - 2005

Keywords

  • Animals
  • Antigens, CD95
  • Apoptosis
  • Cells, Cultured
  • Enzyme Inhibitors
  • I-kappa B Proteins
  • Mice
  • Mitogen-Activated Protein Kinase Kinases
  • Mitogen-Activated Protein Kinases
  • NF-kappa B
  • Recombinant Fusion Proteins
  • Sertoli Cells
  • Signal Transduction
  • Transfection
  • Tumor Necrosis Factor-alpha
  • p38 Mitogen-Activated Protein Kinases

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