Regulation of the ß-cell inflammasome and contribution to stress-induced cellular dysfunction and apoptosis.
Mol Cell Endocrinol
; 478: 106-114, 2018 12 15.
Article
em En
| MEDLINE
| ID: mdl-30121202
ABSTRACT
ß-Cells may be a source of IL-1ß that is produced as inactive pro-IL-1ß and processed into biologically-active IL-1ß by enzymatic cleavage mediated by the NLRP1-, NLRP3- and NLRC4-inflammasomes. Little is known about the ß-cell inflammasomes. NLRP1-expression was upregulated in islet-cells from T2D-patients and by IL-1ß+IFNγ in INS-1 cells in a histone-deacetylase dependent manner. NLRP3 was downregulated by cytokines in INS-1 cells. NLRC4 was barely expressed and not regulated by cytokines. High extracellular K+ reduced cytokine-induced apoptosis and NO production and restored cytokine-inhibited accumulated insulin-secretion. Basal inflammasome expression was JNK1-3 dependent. Knock-down of the ASC interaction domain common for NLRP1 and 3 improved insulin secretion and ameliorated IL-1ß and/or glucolipotoxicity-induced cell death and reduced cytokine-induced NO-production. Broad inflammasome-inhibition, but not NLRP3-selective inhibition, protected against IL-1ß-induced INS-1 cell-toxicity. We suggest that IL-1ß causes ß-cell toxicity in part by NLRP1 mediated caspase-1-activation and maturation of IL-1ß leading to an autocrine potentiation loop.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estresse Fisiológico
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Apoptose
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Células Secretoras de Insulina
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Inflamassomos
Limite:
Adult
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Animals
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Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article