التفاصيل البيبلوغرافية
| العنوان: |
Endogenous mitochondrial double‐stranded RNA is not an activator of the type I interferon response in human pancreatic beta cells. |
| المؤلفون: |
Coomans de Brachène, Alexandra1 (AUTHOR) alcooman@ulb.ac.be, Castela, Angela1 (AUTHOR), Musuaya, Anyïshai E.1 (AUTHOR), Marselli, Lorella2 (AUTHOR), Marchetti, Piero2 (AUTHOR), Eizirik, Decio L.1,3 (AUTHOR) |
| المصدر: |
Autoimmunity Highlights. 3/27/2021, Vol. 12 Issue 1, p1-10. 10p. |
| مصطلحات موضوعية: |
*PANCREATIC beta cells, *TYPE I interferons, *DOUBLE-stranded RNA, *MITOCHONDRIAL RNA, *ISLANDS of Langerhans |
| مستخلص: |
Background: Type 1 diabetes (T1D) is an autoimmune disease characterized by the progressive destruction of pancreatic beta cells. Interferon-α (IFNα), an antiviral cytokine, is expressed in the pancreatic islets in early T1D, which may be secondary to viral infections. However, not all patients harboring a type I IFN signature present signals of viral infection, suggesting that this response might be initiated by other "danger signals". Accumulation of mitochondrial double-stranded RNA (mtdsRNA; a danger signal), secondary to silencing of members of the mitochondrial degradosome, PNPT1 and SUV3, has been described to activate the innate immune response. Methods: To evaluate whether mtdsRNA represents a "danger signal" for pancreatic beta cells in the context of T1D, we silenced PNPT1 and/or SUV3 in slowly proliferating human insulin-secreting EndoC-βH1 cells and in non-proliferating primary human beta cells and evaluated dsRNA accumulation by immunofluorescence and the type I IFN response by western blotting and RT-qPCR. Results: Only the simultaneous silencing of PNPT1/SUV3 induced dsRNA accumulation in EndoC-βH1 cells but not in dispersed human islets, and there was no induction of a type I IFN response. By contrast, silencing of these two genes individually was enough to induce dsRNA accumulation in fibroblasts present in the human islet preparations. Conclusions: These data suggest that accumulation of endogenous mtdsRNA following degradosome knockdown depends on the proliferative capacity of the cells and is not a mediator of the type I IFN response in human pancreatic beta cells. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
Academic Search Index |
Full Text Finder