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The transcription factor B-cell lymphoma (BCL)-6 modulates pancreatic {beta}-cell inflammatory responses.
- Source :
-
Endocrinology [Endocrinology] 2011 Feb; Vol. 152 (2), pp. 447-56. Date of Electronic Publication: 2010 Dec 29. - Publication Year :
- 2011
-
Abstract
- Type 1 diabetes is a chronic autoimmune disease with a strong inflammatory component. We have previously shown that expression of the transcriptional repressor B-cell lymphoma (BCL)-6 is very low in pancreatic β-cells, which may favor prolonged proinflammatory responses after exposure to the cytokines IL-1β and interferon γ. Here we investigated whether cytokine-induced inflammation and apoptosis can be prevented in β-cells by BCL-6 expression using plasmid, prolactin, and adenoviral approaches. The induction of mild or abundant BCL-6 expression in β-cells by prolactin or an adenoviral BCL-6 expression construct, respectively, reduced cytokine-induced inflammatory responses in a dose-dependent manner through inhibition of nuclear factor-κB activation. BCL-6 decreased Fas and inducible nitric oxide synthase expression and nitric oxide production, but it inhibited the expression of the antiapoptotic proteins Bcl-2 and JunB while increasing the expression of the proapoptotic death protein 5. The net result of these opposite effects was an augmentation of β-cell apoptosis. In conclusion, BCL-6 expression tones down the unrestrained cytokine-induced proinflammatory response of β-cells but it also favors gene networks leading to apoptosis. This suggests that cytokine-induced proinflammatory and proapoptotic signals can be dissociated in β-cells. Further understanding of these pathways may open new possibilities to improve β-cell survival in early type 1 diabetes or after transplantation.
- Subjects :
- Animals
Apoptosis drug effects
Blotting, Western
Cell Line
Cell Survival drug effects
Cell Survival genetics
Colforsin pharmacology
Cytokines pharmacology
Exenatide
Fluorescent Antibody Technique
Insulin-Secreting Cells cytology
Insulin-Secreting Cells drug effects
Male
NF-kappa B genetics
Nitric Oxide Synthase Type II genetics
Peptides pharmacology
Polymerase Chain Reaction
Prolactin pharmacology
Proto-Oncogene Proteins c-bcl-6 genetics
Rats
Rats, Wistar
Venoms pharmacology
fas Receptor genetics
Insulin-Secreting Cells immunology
Insulin-Secreting Cells metabolism
Proto-Oncogene Proteins c-bcl-6 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1945-7170
- Volume :
- 152
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 21190961
- Full Text :
- https://doi.org/10.1210/en.2010-0790