Tags

Type your tag names separated by a space and hit enter

NF-kappaB protects Behçet's disease T cells against CD95-induced apoptosis up-regulating antiapoptotic proteins.
Arthritis Rheum. 2005 Jul; 52(7):2179-91.AR

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-kappaB regulatory proteins were measured using Western blotting and immunohistochemical analyses. To down-regulate NF-kappaB nuclear translocation, BD T lymphocytes were exposed in vitro to thalidomide and subjected to transfection with NF-kappaB 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 up-regulation of the short form of cellular FLIP (cFLIP) and Bcl-x(L) 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 IkappaB was up-regulated, whereas NF-kappaB translocated to the nucleus in BD T cells, suggesting that NF-kappaB activation may modulate the expression of antiapoptotic genes. Interestingly, thalidomide and NF-kappaB small interfering RNA down-regulated cFLIP and Bcl-x(L) expression levels and sensitized BD activated T cells to CD95-induced apoptosis.

CONCLUSION

Taken together, these results indicate that NF-kappaB 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-kappaB 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.

Authors+Show Affiliations

Università di Palermo, Palermo, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15986355

Citation

Todaro, Matilde, et al. "NF-kappaB Protects Behçet's Disease T Cells Against CD95-induced Apoptosis Up-regulating Antiapoptotic Proteins." Arthritis and Rheumatism, vol. 52, no. 7, 2005, pp. 2179-91.
Todaro M, Zerilli M, Triolo G, et al. NF-kappaB protects Behçet's disease T cells against CD95-induced apoptosis up-regulating antiapoptotic proteins. Arthritis Rheum. 2005;52(7):2179-91.
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-kappaB protects Behçet's disease T cells against CD95-induced apoptosis up-regulating antiapoptotic proteins. Arthritis and Rheumatism, 52(7), 2179-91.
Todaro M, et al. NF-kappaB Protects Behçet's Disease T Cells Against CD95-induced Apoptosis Up-regulating Antiapoptotic Proteins. Arthritis Rheum. 2005;52(7):2179-91. PubMed PMID: 15986355.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NF-kappaB protects Behçet's disease T cells against CD95-induced apoptosis up-regulating antiapoptotic proteins. AU - Todaro,Matilde, AU - Zerilli,Monica, AU - Triolo,Giovanni, AU - Iovino,Flora, AU - Patti,Mariella, AU - Accardo-Palumbo,Antonina, AU - di Gaudio,Francesca, AU - Turco,Maria Caterina, AU - Petrella,Antonello, AU - de Maria,Ruggero, AU - Stassi,Giorgio, PY - 2005/6/30/pubmed PY - 2005/8/17/medline PY - 2005/6/30/entrez SP - 2179 EP - 91 JF - Arthritis and rheumatism JO - Arthritis Rheum VL - 52 IS - 7 N2 - 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-kappaB regulatory proteins were measured using Western blotting and immunohistochemical analyses. To down-regulate NF-kappaB nuclear translocation, BD T lymphocytes were exposed in vitro to thalidomide and subjected to transfection with NF-kappaB 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 up-regulation of the short form of cellular FLIP (cFLIP) and Bcl-x(L) 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 IkappaB was up-regulated, whereas NF-kappaB translocated to the nucleus in BD T cells, suggesting that NF-kappaB activation may modulate the expression of antiapoptotic genes. Interestingly, thalidomide and NF-kappaB small interfering RNA down-regulated cFLIP and Bcl-x(L) expression levels and sensitized BD activated T cells to CD95-induced apoptosis. CONCLUSION: Taken together, these results indicate that NF-kappaB 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-kappaB 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. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/15986355/NF_kappaB_protects_Behçet's_disease_T_cells_against_CD95_induced_apoptosis_up_regulating_antiapoptotic_proteins_ L2 - https://doi.org/10.1002/art.21145 DB - PRIME DP - Unbound Medicine ER -