NF-κB protects Behçet's disease T cells against CD95-induced apoptosis up-regulating antiapoptotic proteins

Matilde Todaro, Monica Zerilli, Giovanni Triolo, Flora Iovino, Mariella Patti, Antonina Accardo-Palumbo, Francesca Di Gaudio, Maria Caterina Turco, Antonello Petrella, Ruggero De Maria, Giorgio Stassi

Research output: Contribution to journalArticle

Abstract

Objective. To determine whether prolongation of the inflammatory reaction in patients with Behçet's disease (BD) is related to apoptosis resistance and is associated with the up-regulation of antiapoptotic factors. Methods. The percentage of cell death was evaluated by flow cytometry in peripheral blood mononuclear cells from 35 patients with BD and 30 healthy volunteers. The expression levels of antiapoptotic factors and NF-κB regulatory proteins were measured using Western blotting and immunohistochemical analyses. To down-regulate NF-κB nuclear translocation, BD T lymphocytes were exposed in vitro to thalidomide and subjected to transfection with NF-κB small interfering RNA. Results. Although CD95 is highly expressed in BD T cells, the absence of sensitivity to CD95-induced apoptosis observed may be attributable to the inhibitory action of antiapoptotic genes. Immunoblot analysis for major antiapoptotic proteins showed considerable upregulation of the short form of cellular FLIP (cFLIP) and Bcl-xL in BD activated T cells, while levels of Bcl-2, caspase 3, and caspase 8 in activated T cells from patients with BD were comparable with those in activated T cells from normal donors. Moreover, expression of IKK and IκB was up-regulated, whereas NF-κB translocated to the nucleus in BD T cells, suggesting that NF-κB activation may modulate the expression of antiapoptotic genes. Interestingly, thalidomide and NF-κB small interfering RNA down-regulated cFLIP and Bcl-xL expression levels and sensitized BD activated T cells to CD95-induced apoptosis. Conclusion. Taken together, these results indicate that NF-κB contributes to the regulation of the apoptosis-related factors and death receptors leading to apoptosis resistance in BD T cell subsets. Our results suggest that NF-κB plays a crucial role in the pathogenesis of BD, and that its pharmacologic control could represent a key strategy in modulating specific immune-mediated disease.

Original languageEnglish
Pages (from-to)2179-2191
Number of pages13
JournalArthritis and Rheumatism
Volume52
Issue number7
DOIs
Publication statusPublished - Jul 2005

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

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    Todaro, M., Zerilli, M., Triolo, G., Iovino, F., Patti, M., Accardo-Palumbo, A., Di Gaudio, F., Turco, M. C., Petrella, A., De Maria, R., & Stassi, G. (2005). NF-κB protects Behçet's disease T cells against CD95-induced apoptosis up-regulating antiapoptotic proteins. Arthritis and Rheumatism, 52(7), 2179-2191. https://doi.org/10.1002/art.21145