The Role Of P-STAT3/IL-17 In The Pathogenesis Of Idiopathic Inflammatory Myopathy

Objective:This study was performed to investigate the levels of phosphorylated signal transduction and activator of transcription 3(p-STAT3)and interleukin 17(IL-17)expression in the muscle tissue of patients with idiopathic inflammatory myopathy(IIM)and explore their roles in the pathogenesis of myositis.Methods:The expression levels of p-STAT3 and IL-17 in the muscle of 28 patients with IIM after muscle biopsy and autoantibody detection and 12 control patients were examined using Western blotting and immunohistochemical analyses.Serum IL-6 levels were detected by enzyme-linked immunosorbent assay(ELISA).Data regarding clinical features and laboratory findings were collected.Disease activity was evaluated using visual analogue scales for myositis disease activity(MYOACT)on admission.The muscle p-STAT3 and IL-17 levels were analysed and compared with clinical manifestations,laboratory data,serum IL-6 and indicators of disease activity.The nonparametric test was used to compare the expression differences of p-STAT3 and IL-17in muscle tissue between the two groups.Chi-square test and Spearman rank correlation were used to analyze the relationship among the levels of p-STAT3 and IL-17 in muscle of IIM group and clinical characteristics,laboratory markers,IL-6,and activity scores.Data were analyzed using SPSS 26.0 and plotted using Graph Pad Prism 9.0.P<0.05 was considered to be statistically significant.Results:In this study,compared with the control group,the serum levels of ALT,AST,CK,CK-MB,HBD,LDH and ESR in the IIM group were significantly higher,while the red blood cell count,hemoglobin,and albumin were lower,and the difference was statistically significant(P<0.05).The difference in age,gender,BMI,white blood cell count,platelet count between IIM patients and HCs was not statistically significant(P>0.05).Both muscle p-STAT3 and IL-17 levels were significantly higher in IIM patients than in Controls and in the DM patients than ASS patients by using Western Blot,the difference was statistically significant(P<0.05).Both muscle p-STAT3 and IL-17 levels were significantly higher in IIM patients than in Controls by using immunohistochemistry,and the distribution of p-STAT3 and IL-17 positive expression was different in DM and ASS.In DM,it is mainly distributed in the atrophic and necrotic myofibers around muscle bundles and inflammatory cells around vessel walls,while in ASS,it is distributed in the mononuclear cells around the muscle cells.The percentages of p-STAT3 and IL-17 expression were significantly greater in the IIM group than in the HCs(P<0.05),but there was no significant difference in the positive expression rates of muscle p-STAT3 and IL-17 between the DM and ASS groups.Serum IL-6 levels were significantly higher in IIM patients than in Controls by using ELISA,the difference was statistically significant(P<0.05),but there was no significant difference between the DM and ASS groups(P>0.05).The muscle p-STAT3 and IL-17 level and serum IL-6 levels of IIM patients were significantly positively correlated(r_s=0.418,P=0.027;r_s=0.579,P=0.001 and r_s=0.419,P=0.027).The p-STAT3 level was positively correlated with serum AST,CK,LDH,HBD,MYOACT-total activity,MYOACT-general condition,MYOACT-skin mucous membrane and MYOACT-muscle symptoms(r_s=0.622,P<0.001;r_s=0.714,P<0.001;r_s=0.590,P=0.001;r_s=0.555,P=0.003;r_s=0.585,P=0.001;r_s=0.416,P=0.028;r_s=0.438,P=0.02 and r_s=0.510,P=0.006).The p-STAT3 level was higher in patients with muscle weakness and skin lesions,and the difference was statistically significant(P<0.05).The IL-17 level was positively correlated with AST,CK,ESR,MYOACT-total activity,MYOACT-general condition,MYOACT-muscle symptoms(r_s=0.561,P=0.002;r_s=0.482,P=0.020;r_s=0.506,P=0.006;r_s=0.498,P=0.007 and r_s=0.453,P=0.016).The IL-17 level was higher in patients with muscle weakness,dysphagia and skin lesions,and the difference was statistically significant(P<0.05).The IL-6 level was positively correlated with AST,HBD,and MYOACT-general condition(r_s=0.461,P=0.013;r_s=0.482,P=0.020;r_s=0.454,P=0.0048).The IL-6 level was higher in patients with muscle weakness and the difference was statistically significant(P<0.05).Conclusion:The levels of p-STAT3 and IL-17 in the muscle of the IIM group were significantly increased,and were positively correlated with serum IL-6,myocardial enzymes and disease activity,suggesting that the p-STAT3/IL-17 pathway may be involved in the process of muscle inflammation,muscle necrosis and perivascular inflammation of IIM,and it may produce skin lesions.The p-STAT3/IL-17 may be a potential therapeutic target for IIM.