Mechanisms of influenza A virus-induced macrophage inflammatory in-jury through IL-6/STAT3 signaling loop and intervention effects of Ma-Xing-Shi-Gan decoction
10.3969/j.issn.1000-4718.2025.11.016
- VernacularTitle:基于IL-6/STAT3信号环路探讨流感病毒所致巨噬细胞炎性损伤的机制及麻杏石甘汤的作用
- Author:
Chunjing CHEN
1
;
Ling LI
1
;
Fangguo LU
1
;
Jue HU
1
;
Xianggang ZHANG
1
;
Huihui LIU
1
;
Li LIANG
1
Author Information
1. 湖南中医药大学,湖南 长沙 410208
- Publication Type:Journal Article
- Keywords:
influenza A virus;
influenza-associated encephalopathy;
Ma-Xing-Shi-Gan decoction;
IL-6/STAT3 signaling loop;
immunopathological damage
- From:
Chinese Journal of Pathophysiology
2025;41(11):2210-2220
- CountryChina
- Language:Chinese
-
Abstract:
AIM:This study aims to explore the mechanisms of influenza A virus(IAV)-induced macrophage inflammatory injury based on the interleukin-6(IL-6)/signal transducer and activator of transcription 3(STAT3)signaling loop and investigate the intervention effects of Ma-Xing-Shi-Gan decoction(MXSGD)-medicated serum.METHODS:RAW264.7 and BV2 cells were divided into control,Janus kinase(JAK)/STAT signaling pathway activator,inhibitor,model,oseltamivir,antiviral particle,and MXSGD groups.After IAV modeling and serum interventions,the cells were cultured for 24 and 48 h,and the indicators were detected and analyzed.ELISA,RT-qPCR,Western blot,and immuno-fluorescence assay were used to detect the secretion levels of IL-6 in the cell culture supernatant,IL-6 and STAT3 mRNA expressions,protein expression of STAT3,and expression levels of phosphorylated STAT3(p-STAT3),respectively.Pearson correlation analysis was used to evaluate the correlation between p-STAT3 and IL-6 in the two cell types.A co-cul-ture model of the two cells was constructed,and the secretion levels of IL-6 in the cell culture supernatant was measured.Molecular docking analyses were performed for STAT3 and MXSGD.RESULTS:After IAV simulation,the secretion lev-els of IL-6 in the cell culture supernatant,mRNA expression levels of IL-6 and STAT3,and protein expression levels of STAT3 and p-STAT3 in both cell lines were elevated(P<0.05 or P<0.01).Pearson correlation analysis revealed that p-STAT3 expression was positively correlated with IL-6 expression.The secretion levels of IL-6 in the co-culture model in-creased(P<0.01).MXSGD down-regulated the secretion levels of IL-6 in the cell culture supernatant mRNA,expression levels of IL-6 and STAT3,and protein expression levels of STAT3 and p-STAT3 in two kinds of cells(P<0.05 or P<0.01),and inhibited the secretion levels of IL-6 in co-culture models.STAT3 demonstrated good binding energies for liquiritin,amygdalin,and ephedrine.CONCLUSION:IAV can induce inflammatory injury in macrophages,and its mechanism may be related to activation of the IL-6/STAT3 signaling loop.MXSGD may alleviate the pathogenic effects of IAV by modulating the signaling loop.
