title: Ethyl pyruvate attenuated coxsackievirus B3-induced acute viral myocarditis by suppression of HMGB1/RAGE/NF-ΚB pathway.
abstract: Inflammation plays important roles in the pathogenesis of coxsackievirus B3 (CVB3)-induced acute viral myocarditis (AVMC). Ethyl pyruvate (EP) has been shown to be an anti-inflammatory agent. High mobility group box 1 (HMGB1)/receptor for advanced glycation end product (RAGE)/nuclear factor (NF)-ΚB pathway has close relation with inflammatory responses. Here, we investigated the effects of EP on CVB3-induced AVMC and potential mechanisms. The mice with AVMC were treated with EP (40 or 80 mg/kg/day) from day 5 to day 7 post-infection. EP significantly decreased the mortality of mice with AVMC. H&E staining and immunohistochemistry for HMGB1 demonstrated less inflammatory lesions and fewer abnormal location of HMGB1 in the hearts of AVMC mice receiving EP. Immuoblot showed that EP significantly inhibited the levels of HMGB1, RAGE, phospho(p)-NF-ΚB and p-I-ΚBα, and raised I-ΚBα expression in the hearts of AVMC mice. Furthermore, real-time PCR and Elisa displayed decreased levels of HMGB1, TNF-α, IL-1β, IL-17 and increased levels of IL-10 in the hearts and serum of AVMC mice treated with EP. Our findings suggest that EP protects against CVB3-induced AVMC that is associated with inhibition of HMGB1/RAGE/NF-ΚB pathway.
authors.affiliation: Key Laboratory of Viral Heart Diseases, Ministry of Public Health, Shanghai, 200032 China.|Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai, 200032 China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Key Laboratory of Viral Heart Diseases, Ministry of Public Health, Shanghai, 200032 China.|Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai, 200032 China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai, 200032 China.
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai, 200032 China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
authors.affiliation: Key Laboratory of Viral Heart Diseases, Ministry of Public Health, Shanghai, 200032 China.|Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai, 200032 China.
authors.forename: Guijian
authors.initials: G
authors.lastname: Liu
authors.affiliation: Key Laboratory of Viral Heart Diseases, Ministry of Public Health, Shanghai, 200032 China.|Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai, 200032 China.
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai, 200032 China.
authors.forename: Yangang
authors.initials: Y
authors.lastname: Su
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai, 200032 China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Viral Heart Diseases, Ministry of Public Health, Shanghai, 200032 China.|Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai, 200032 China.
authors.forename: Ruizhen
authors.initials: R
authors.lastname: Chen
keywords: Coxsackievirus B3; Ethyl pyruvate; High mobility group box 1; Myocarditis; Nuclear factor-ΚB; Receptor for advanced glycation end product