Advanced search
1 file | 419.31 KB Add to list

Double-stranded RNA induces pancreatic beta-cell apoptosis by activation of the toll-like receptor 3 and interferon regulatory factor 3 pathways

(2008) DIABETES. 57(5). p.1236-1245
Author
Organization
Abstract
OBJECTIVE-Viral infections contribute to the pathogenesis of type 1 diabetes. Viruses, or viral products such as double-stranded RNA (dsRNA), affect pancreatic beta-cell survival and trigger autoimmunity by unknown mechanisms. We presently investigated the mediators and downstream effectors of dsRNA-induced beta-cell death. RESEARCH DESIGN AND METHODS-Primary rat beta-cells and islet cells from wild-type, toll-like receptor (TLR) 3, type I interferon receptor (IFNAR1), or interferon regulatory factor (IRF)-3 knockout mice were exposed to external dsRNA (external polyinosinic-polycytidylic acid [PICex]) or were transfected with dsRNA ([PICin]). RESULTS-TLR3 signaling mediated PICex-induced nuclear factor-kappa B (NF-kappa B) and IRF-3 activation and beta-cell apoptosis. PICin activated NF-kappa B and IRF-3 in a TLR3-independent manner, induced eukaryotic initiation factor 2 alpha phosphorylation and triggered a massive production of interferon (IFN)-beta.This contributed to beta-cell death, as islet cells from IFNAR1(-/-) or IRF 3(-/-) mice were protected against PICin-induced apoptosis. CONCLUSIONS-PICex and PICin trigger beta-cell apoptosis via the TLR-3 pathway or IRF-3 signaling, respectively. Execution of PICin-mediated apoptosis depends on autocrine effects of type
Keywords
ENDOPLASMIC-RETICULUM STRESS, TYPE-1 DIABETES-MELLITUS, NITRIC-OXIDE, INDUCED GENES, MESSENGER-RNA, MECHANISMS, GAMMA, EXPRESSION, VIRUS, NF-KAPPA-B

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 419.31 KB

Citation

Please use this url to cite or link to this publication:

MLA
Dogusan, Zeynep, Monica García, Daisy Flamez, et al. “Double-stranded RNA Induces Pancreatic Beta-cell Apoptosis by Activation of the Toll-like Receptor 3 and Interferon Regulatory Factor 3 Pathways.” DIABETES 57.5 (2008): 1236–1245. Print.
APA
Dogusan, Z., García, M., Flamez, D., Alexopouiou, L., Goldman, M., Gysemans, C., Mathieu, C., et al. (2008). Double-stranded RNA induces pancreatic beta-cell apoptosis by activation of the toll-like receptor 3 and interferon regulatory factor 3 pathways. DIABETES, 57(5), 1236–1245.
Chicago author-date
Dogusan, Zeynep, Monica García, Daisy Flamez, Lena Alexopouiou, Michel Goldman, Conny Gysemans, Chantal Mathieu, Claude Libert, Décio L Eizirik, and Joanne Rasschaert. 2008. “Double-stranded RNA Induces Pancreatic Beta-cell Apoptosis by Activation of the Toll-like Receptor 3 and Interferon Regulatory Factor 3 Pathways.” Diabetes 57 (5): 1236–1245.
Chicago author-date (all authors)
Dogusan, Zeynep, Monica García, Daisy Flamez, Lena Alexopouiou, Michel Goldman, Conny Gysemans, Chantal Mathieu, Claude Libert, Décio L Eizirik, and Joanne Rasschaert. 2008. “Double-stranded RNA Induces Pancreatic Beta-cell Apoptosis by Activation of the Toll-like Receptor 3 and Interferon Regulatory Factor 3 Pathways.” Diabetes 57 (5): 1236–1245.
Vancouver
1.
Dogusan Z, García M, Flamez D, Alexopouiou L, Goldman M, Gysemans C, et al. Double-stranded RNA induces pancreatic beta-cell apoptosis by activation of the toll-like receptor 3 and interferon regulatory factor 3 pathways. DIABETES. 2008;57(5):1236–45.
IEEE
[1]
Z. Dogusan et al., “Double-stranded RNA induces pancreatic beta-cell apoptosis by activation of the toll-like receptor 3 and interferon regulatory factor 3 pathways,” DIABETES, vol. 57, no. 5, pp. 1236–1245, 2008.
@article{428314,
  abstract     = {OBJECTIVE-Viral infections contribute to the pathogenesis of type 1 diabetes. Viruses, or viral products such as double-stranded RNA (dsRNA), affect pancreatic beta-cell survival and trigger autoimmunity by unknown mechanisms. We presently investigated the mediators and downstream effectors of dsRNA-induced beta-cell death.
RESEARCH DESIGN AND METHODS-Primary rat beta-cells and islet cells from wild-type, toll-like receptor (TLR) 3, type I interferon receptor (IFNAR1), or interferon regulatory factor (IRF)-3 knockout mice were exposed to external dsRNA (external polyinosinic-polycytidylic acid [PICex]) or were transfected with dsRNA ([PICin]).
RESULTS-TLR3 signaling mediated PICex-induced nuclear factor-kappa B (NF-kappa B) and IRF-3 activation and beta-cell apoptosis. PICin activated NF-kappa B and IRF-3 in a TLR3-independent manner, induced eukaryotic initiation factor 2 alpha phosphorylation and triggered a massive production of interferon (IFN)-beta.This contributed to beta-cell death, as islet cells from IFNAR1(-/-) or IRF 3(-/-) mice were protected against PICin-induced apoptosis.
CONCLUSIONS-PICex and PICin trigger beta-cell apoptosis via the TLR-3 pathway or IRF-3 signaling, respectively. Execution of PICin-mediated apoptosis depends on autocrine effects of type},
  author       = {Dogusan, Zeynep and García, Monica and Flamez, Daisy and Alexopouiou, Lena and Goldman, Michel and Gysemans, Conny and Mathieu, Chantal and Libert, Claude and Eizirik, Décio L and Rasschaert, Joanne},
  issn         = {0012-1797},
  journal      = {DIABETES},
  keywords     = {ENDOPLASMIC-RETICULUM STRESS,TYPE-1 DIABETES-MELLITUS,NITRIC-OXIDE,INDUCED GENES,MESSENGER-RNA,MECHANISMS,GAMMA,EXPRESSION,VIRUS,NF-KAPPA-B},
  language     = {eng},
  number       = {5},
  pages        = {1236--1245},
  title        = {Double-stranded RNA induces pancreatic beta-cell apoptosis by activation of the toll-like receptor 3 and interferon regulatory factor 3 pathways},
  url          = {http://dx.doi.org/10.2337/db07-0844},
  volume       = {57},
  year         = {2008},
}

Altmetric
View in Altmetric
Web of Science
Times cited: