The Effect Of PolyI: C On Fas And Fas Ligand Expression In Pancreas Of NOD Mice

Objective: To study the effects of PolyI:C (Polyinosinic polycytidylic acid) on the incidence of diabetes and insulitis in the NOD (non-obese diabetic) mice, and change of Fas/ FasL protein and mRNA expression in pancreatic cells.Methods: 100 female 4-week-old NOD mices were randomly divided into two parts. Part one(24 mices): The mices were killed respectively at 4th and 15th week. Insulitis scores were observed by HE straning. Expression of Fas, FasL protein were measured by immunohistochemical straining in islet cells. Part two(76 mices): Beginning from four weeks of age, PolyI:C group (n=36) was administered PolyI:C 0.05μg/g body by intraperitoneal (i.p) injection one time every other day for four weeks, and PBS group (n=40) was administered PBS only with the same method. At fifteen weeks of age, the degree of insulitis was observed, Fas andFas Ligand(FasL) protein expression on islets of Langerhans in both groups of NOD mice were examined by SP immunohistochemical techniques, and the levels of Fas and FasL mRNA in pancreata were detected by method of reverse transcription-polymerase chain reaction (RT-PCR). The incidence of diabetes was detected at age of twenty four weeks.Result: Expression of Fas protein at 15th week was stronger than 4th week in NOD mice. The incidence of diabetes in PolyI:C group (11.1%) was obviously less than that in the control group (72.7%). Hisological examination revealed that the index of infiltrated islets and the severity of insulitis in PolyI:C group were also lower than that in PBS group (p<0.01). Fas protein expression in islets and mRNA expression in pancreatic cells of PolyI:C group were significantly downregulated compared with PBS group (p<0.01). FasL protein and mRNA were not obviously different between two groups.Conclusion: These results show that PolyI:C can prevent spontaneous type 1 diabetes in NOD mice, and the effect of PolyI:C may be related to downregulating the Fas expression in pancreaticcells. Fas/FasL play the role in pathogenesis of type I diabetes in NOD mice.