ISSN:
0730-2312
Keywords:
IFN- and TNF-pancreatic beta cell function
;
insulin secretion and content
;
effects of IFN- and TNF-reovirus infection
;
major histocompatibility complex protein expression
;
RIN-m5F cells major histocompatibility complex protein expression
;
major histocompatibility complex
;
mRNA levels
;
Life and Medical Sciences
;
Cell & Developmental Biology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
Notes:
Insulin-dependent (type 1) diabetes mellitus (IDDM) is due to the selective autoimmune-mediated destruction of pancreatic beta cells possibly initiated by viruses. To elucidate the possible role of viruses and cytokines in the pathogenesis of IDDM, we have examined the effect of reovirus infection on beta cell major histocompatibility complex (MHC) expression and the effect of interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α) on beta cell function in vitro. Infection of RIN-m5F (rat insulinoma) cells with reovirus-1 or reovirus-3 was associated with a tenfold increase in class 1 MHC protein and mRNA expression. Reovirus infection did not induce the expression of class 11 MHC by RIN-m5F cells. Exposure of reovirus to ultraviolet light almost completely abolished its ability to induce class 1 MHC protein expression on infected cells.Murine islets cultured for 3 days with IFN-γ and/or TNF-α had a significantly reduced insulin response to glucose, which was more marked with a combination of the cytokines. During 6 days of culture in IFN-γ plus TNF-α islets underwent noticeable degeneration associated with an 80% reduction in insulin content. These findings together with previous data suggest viruses and cytokines may have multiple roles in beta cell destruction, indirectly through enhanced MHC protein expression and directly through functional impairment and loss of viability.
Additional Material:
4 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jcb.240400107
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