Iridin regulates PD-1/PD-L1 pathway and enhances antiviral immune level in mice with viral myocarditis
Objective:To investigate the effect of iridin on enhancing antiviral immune effect in mice with viral myocarditis by regulating programmed death factor-1(PD-1)/programmed death factor ligand-l(PD-L1)pathway.Methods:Fifty C57BL/6 mice were inoculated intraperitoneally with Coxsackie virus B3(CVB3)to construct mouse model of viral myocarditis.Successfully modeled mice were randomly divided into model group,iridin low,medium and high doses groups and positive control group.Another 10 C57BL/6 mice were recorded as blank control group.Positive control group was given 10 000 U/g interferon by intraperitoneal injec-tion,irisin low,medium and high dosed groups were given 30,60 and 120 μg/kg iridin by intraperitoneal injection,and blank control group and positive control group were given the same amount of normal saline once a day for 2 weeks.HE staining was used to observe pathological changes of mouse myocardium.Virus titer in mouse myocardium was detected by plaque forming unit(PFU)method.Pro-portion of T lymphocyte subsets(CD4+T,CD8+T,NK cells)and CD4+T/CD8+T were detected by flow cytometry.Inflammatory cyto-kines IL-6,IL-17,TNF-α and IFN-γ levels in mouse myocardium were detected by ELISA.RT-qPCR was used to detect expression of PD-1 mRNA in T lymphocytes and expression of PD-L1 mRNA in myocardium of mouse.Western blot was used to detect expression of PD-1 protein in T lymphocytes and expression of PD-L1 protein in myocardium of mice.Results:Compared with blank control group,myocardial tissue structure of model group changed significantly,with a large number of inflammatory cell infiltration and focal necro-sis,pathological score,virus titer,levels of inflammatory cytokines IL-6,IL-17,TNF-α and IFN-γ,and PD-L1 mRNA and protein expressions in myocardial tissue were increased,proportion of peripheral blood CD8+T lymphocytes and expression of PD-1 mRNA and protein in T lymphocytes were increased,while proportion of peripheral blood CD4+T lymphocytes,NK cells and CD4+T/CD8+T were decreased,the differences were statistically significant(P<0.05).Compared with model group,pathological changes of myocardial tissue in positive control group and low,medium and high doses groups of irisin were reduced in varying degrees.Pathological score,virus titer,levels of inflammatory cytokines IL-6,IL-17,TNF-α and IFN-γ,and PD-L1 mRNA and protein expression in myocardial tissue were decreased,the proportion of peripheral blood CD8+T lymphocytes and expression of PD-1 mRNA and protein in T lymphocytes were decreased,while the proportion of peripheral blood CD4+T lymphocytes,NK cells and CD4+T/CD8+T were increased,effect of iri-din was as a dose-dependent manner,the differences were statistically significant(P<0.05).Conclusion:Iridin can enhance the anti-viral immune effect of viral myocarditis mice.It is speculated that iridin can improve the proportion imbalance of T lymphocyte subsets in peripheral blood of mice and improve the immune function of the body by inhibiting the activation of PD-1/PD-L1 pathway.
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