C/EBP homologous protein contributes to cytokine-induced pro-inflammatory responses and apoptosis in β-cells.

Détails

ID Serval
serval:BIB_DC763804A6EE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
C/EBP homologous protein contributes to cytokine-induced pro-inflammatory responses and apoptosis in β-cells.
Périodique
Cell Death and Differentiation
Auteur(s)
Allagnat F., Fukaya M., Nogueira T.C., Delaroche D., Welsh N., Marselli L., Marchetti P., Haefliger J.A., Eizirik D.L., Cardozo A.K.
ISSN
1476-5403 (Electronic)
ISSN-L
1350-9047
Statut éditorial
Publié
Date de publication
2012
Volume
19
Numéro
11
Pages
1836-1846
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: ppublish
Résumé
Induction of the C/EBP homologous protein (CHOP) is considered a key event for endoplasmic reticulum (ER) stress-mediated apoptosis. Type 1 diabetes (T1D) is characterized by an autoimmune destruction of the pancreatic β-cells. Pro-inflammatory cytokines are early mediators of β-cell death in T1D. Cytokines induce ER stress and CHOP overexpression in β-cells, but the role for CHOP overexpression in cytokine-induced β-cell apoptosis remains controversial. We presently observed that CHOP knockdown (KD) prevents cytokine-mediated degradation of the anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2) and myeloid cell leukemia sequence 1 (Mcl-1), thereby decreasing the cleavage of executioner caspases 9 and 3, and apoptosis. Nuclear factor-κB (NF-κB) is a crucial transcription factor regulating β-cell apoptosis and inflammation. CHOP KD resulted in reduced cytokine-induced NF-κB activity and expression of key NF-κB target genes involved in apoptosis and inflammation, including iNOS, FAS, IRF-7, IL-15, CCL5 and CXCL10. This was due to decreased IκB degradation and p65 translocation to the nucleus. The present data suggest that CHOP has a dual role in promoting β-cell death: (1) CHOP directly contributes to cytokine-induced β-cell apoptosis by promoting cytokine-induced mitochondrial pathways of apoptosis; and (2) by supporting the NF-κB activation and subsequent cytokine/chemokine expression, CHOP may contribute to apoptosis and the chemo attraction of mononuclear cells to the islets during insulitis.
Pubmed
Web of science
Open Access
Oui
Création de la notice
08/11/2012 19:22
Dernière modification de la notice
20/08/2019 17:01
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