Protective effects of Wuwei Xiaodu Drink against chronic osteomyelitis through Foxp3^(+)CD25^(+)CD4^(+) Treg cells via the IL-2/STAT5 signaling pathway
作者机构：Department of OrthopedicsTongde Hospital of Zhejiang ProvinceHangzhou 310012China
出 版 物：《Chinese Journal of Natural Medicines》 (中国天然药物（英文版）)
年 卷 期：2022年第20卷第3期
页 面：185-193页
核心收录：
学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1002[医学-临床医学] 10[医学] 100602[医学-中西医结合临床]
基 金：the National Natural Science Foundation of China(No.81603644) the Natural Science Foundation of Zhejiang Province(No.LY20H270002) Zhejiang TCM Science and Technology Program(No.2020ZQ006) Zhejiang Medical and Health Science and Technology Program(No.2020RC048).
主 题：Chronic osteomyelitis Tregs Immunodepression Wuwei Xiaodu Drink
摘 要：To explore the effectiveness and safety of a Chinese medicinal decoction Wuwei Xiaodu Drink(WWXDD)in inhibiting chronic osteomyelitis via regulatory T cells signaling.The effective constitutes of WWXDD and osteomyelitis related genes were screened.Target proteins were cross-validated using the Venny database.GO function and KEGG pathway analysis were performed for target proteins,while pharmacological network was constructed.The bone properties were analyzed by HE staining and the concentrations of immune factors were measured by ELISA.The expression of CTLA-4 and Foxp3 mRNA and STAT5,p-STAT5,CTLA-4 and Foxp3 protein were detected using Real-time PCR and Western blot,respectively.FACS was used to analyze the percentages of cells.A total of 117 genes overlapped between 785 target genes of the active compounds of WWXDD and 912 osteomyelitis related genes.Inflammation-related genes,including IL-6,TNFα,IL-1βand IL-2 showed high connection degree in the drug-compound-disease-target network.GO function and KEGG pathway analysis revealed that 117 intersection genes mainly enriched in virus infection related pathways,immune related pathways and chemokine signaling pathway.Furthermore,the development of chronic osteomyelitis was suppressed in model rats after treatment with WWXDD.Meanwhile,the concentrations of IL-2 and CD4^(+)CD25^(+)Foxp3 Treg perr centages together with the levels of p-STAT5,CTLA-4 and Foxp3 were also down-regulated.Furthermore,IL-2 and WWXDD drug-containing serum exhibited opposite effects on regulating IL-2,IL-10,TGF-β1,Foxp3,CTLA4 and STAT5.In addition,a STAT5 phosphorylation inhibitor suppressed the expression of Foxp3 and CTLA-4.WWXDD can treat chronic osteomyelitis through suppressing the main regulating factors of Tregs and interfere its immunodepression.Our results bring a new solution for chronic osteomyelitis.
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