The Effect Of IL-27 On The Expression Of Inflammatory Factors In Coronary Heart Disease Through JAK-STAT Signaling Pathway

BackgroundAccording to "China cardiovascular disease report 2018",with the change of environment and diet habits,the mortality rate of cardiovascular disease in China is relatively high,accounting for more than 40%of the death causes of urban and rural residents,and the number of patients will continue to increase rapidly in the next decade[1].Coronary heart disease(CHD)is also known as coronary atherosclerotic heart disease.Atherosclerosis(AS),vascular endothelial cell injury and thrombosis are the main pathological basis of CHD.Inflammation is known to play an important role in the development of CHD.Overexpression of immune cells and immune molecules can cause the expression of T cells imbalance and promote the development of atherosclerosis.The inflammatory cytokine interleukin-17(IL-17)produced by T cells can directly participate in the inflammatory response of CHD.Preliminary experiments showed that interleukin-27(IL-27)may have a regulatory effect on the expression of IL-17.But there are still few studies on the mechanism of IL-27 in CHD at home and abroad,and the specific pathway of action is still unclear.Signal transduction and activator of transcription(STAT)binding sites are known on the IL-27 receptor.After binding with the corresponding receptor,IL-27 activates STAT as a ligand and then influences the transcription and expression of downstream target genes through the Janus kinase(JAK)/STAT signaling pathway[2-3].Programmed death ligand 1(PD-L1),as a downstream signal molecule of JAK/STAT,can mediate the functional inhibition and depletion of T cells after activation,participate in the inflammatory response of CHD,and maintain the immune self-stability of the body[4].ObjectiveIn this study,the expression changes of STAT1 and STAT3 mRNA,PD-L1 protein and interleukin-17(IL-17)in peripheral blood lymphocytes of patients with CHD before and after treatment with IL-27 were compared and analyzed to explore the specific role of IL-27 in the pathogenesis of CHD.MethodsSelected 120 patients with CHD admitted to our hospital from January 2019 to October 2019 as the experimental group,and 40 healthy subjects as the control group.Peripheral blood mononuclear cells(PBMC)were collected from all subjects,and the experimental group included the stable angina pectoris(SA)group,the unstable angina pectoris(UA)group and the acute myocardial infarction(AMI)group.The expression of STAT1 and STAT3 mRNA in patients and healthy subjects were detected by Polymerase Chain Reaction(PCR).The expression of PD-L1 and IL-17 in patients and healthy subjects were detected by Flow Cytometry.After PBMCs of patients treated with 50ng/ml recombinant IL-27,observed the expression changes of STAT1 and STAT3 mRNA,PD-L1,IL-17 in each experimental group than that before the treatment.Results(1)The relative expression levels of STAT1 mRNA in SA group,UA group and AMI group were all lower the those in healthy control group(P<0.05).After the treatment with IL-27,the relative expression of STAT1 mRNA in each experimental group was significantly higher than that before the treatment(P<0.05).(2)There were no statistically significant differences in the relative expression levels of STAT3 mRNA in SA group,UA group and AMI group than those in healthy control group(P>0.05).After the treatment with IL-27,the relative expression of STAT3 mRNA in each experimental group increased compared with that before the treatment(P<0.05).(3)The expression levels of PD-L1 in SA group,UA group and AMI group were higher than those in healthy control group(P<0.05).After the treatment with IL-27,the expression of PD-L1 protein in each experimental group was increased compared with that before treatment(P<0.05).(4)The expression levels of IL-17 in UA group and AMI group were significantly higher than those in healthy control group(P<0.05),and there was no statistically significant difference in the increase of SA group(P>0.05).After the treatment with IL-27,the expression of IL-17 in each experimental group was decreased compared with that before treatment(P<0.05).ConclusionIL-27 may play a role in CHD mainly by regulating the STAT1 signaling pathway.By upregulating the expression of STAT1 mRNA,IL-27 stimulates the expression of the downstream signaling molecule PD-L1,thereby inhibits the expression of inflammatory factor IL-17 and alleviates the inflammatory response of CHD.As an important immunosuppressive cytokine,IL-27 may become a new therapeutic target for CHD.