SUN Liao, et al. Dynamic changes of FasL/Fas apoptosis pathway in islets of NOD mice. [J]. Journal of Chongqing Medical University (3):333-336(2005) DOI: 10.13406/j.cnki.cyxb.2005.03.007.
Dynamic changes of FasL/Fas apoptosis pathway in islets of NOD mice
Objective:To investigate expression of cytokines and apoptosis factors in islets of female NOD mice at different weeks of age.Methods:54 female NOD mice were randomly divided into three groups(C1
C2
C3)and each group consisted of 18 mice.The mice were killed respectively at 4th
15th
30th week (of onset of diabetes)
and their panreases were removed.The levels of expression of cytokines and apoptosis factors mRNA of the pancreas were detected by RT-PCR.The expressions of cytokines and apoptosis factors protein were measured by using immunohistochemical method.Insulitis scores were observed by HE staining.Results:Expressions of Fas and IFN-γ mRNA in pancreas were stronger in C3 vs C1 or C2
in C2 vs C1(P<0.05).No difference in expression of IL-10 mRNA of pancreas was found in three groups.FasL and CPP32 mRNA in pancreas were more strongly in C2 and C3 than in C1 (FasL
P<0.05;CPP32
P<0.01).Positive correlations existed respectively between levels of Fas
CPP32 mRNA and IFN-γ mRNA of pancreas(γ=0.677
0.530)
but no correlations exited between the apoptosis factors and IL-10mRNA(γ=-0.427
-0.464).There were no correlations between FasL mRNA and IFN-γmRNA or IL-10mRNA(γ=0.306
-0.390).Immunohistochemical staining indicated that strong positive expression of FasL was observed in islet cells in three groups(P>0.05).Expressions of Fas and CPP32 were stronger in islet cells in C2 and C3 vs C1(P<0.05).Levels of all apoptosis factors were not significantly different in infiltrating inflammatory cells between C2 and C3.Conclusion:Th1 cytokines IFN-γ play a main role in pathogenesis of type 1 diabetes;FasL/Fas system participates in destruction of β cells in NOD mice;IFN-γ can promote activation of FasL/Fas apoptosis pathway on β cells.