Document Detail


RNase L contributes to experimentally induced type I diabetes onset in mice.
MedLine Citation:
PMID:  25287058     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The cause of type I diabetes continues to be a focus of investigation. Studies have revealed that interferon (IFN)-ą in pancreatic islets after viral infection or treatment with double-stranded RNA (dsRNA), a mimic of viral infection, is associated with the onset of type I diabetes. However, how IFN-ą contributes to the onset of type I diabetes is obscure. In this study, we found that 2-5A dependent RNase L (RNase L), an IFN-ą-inducible enzyme that functions in the antiviral and antiproliferative activities of IFN, played an important role in dsRNA-induced onset of type I diabetes. By using RNase L deficient, rat insulin promoter (RIP)-B7.1 transgenic mice which are more vulnerable to environmental harmful factors such as viral infection, we demonstrated that deficiency of RNase L in mice resulted in a significant delay of diabetes onset induced by polyinosinic:polycytidylic acid (poly I:C), a type of synthetic dsRNA, and streptozotocin (STZ), a drug which can artificially induce type I-like diabetes in experimental animals. Immunohistochemical staining showed that the population of infiltrated CD8+ T-cells was remarkably reduced in the islets of RNase L deficient mice, suggesting that RNase L may contribute to type I diabetes onset through regulating immune responses. Furthermore, RNase L was responsible for the expression of certain proinflammatory genes in the pancreas in induced conditions. Our findings provide new insight into the molecular mechanism underlying ß-cells destruction and may suggest novel therapeutic strategies for treatment and prevention of the disease based on the selective regulation and inhibition of RNase L.
Authors:
Aimin Zhou; Chun Zeng; Xin Yi; Danny Zipris; Hongli Liu; Lin Zhang; Qiaoyun Zheng; Krishnamurthy Malathi; Ge Jin
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-10-6
Journal Detail:
Title:  The Journal of endocrinology     Volume:  -     ISSN:  1479-6805     ISO Abbreviation:  J. Endocrinol.     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-10-7     Completed Date:  -     Revised Date:  2014-10-8    
Medline Journal Info:
Nlm Unique ID:  0375363     Medline TA:  J Endocrinol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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