Proteasome inhibitors decrease IL-6 and TNF-α levels in mouse acute viral myocarditis

Abstract

Abstract:

AIM:To investigate the effect of proteasome inhibitor in mice with inflammatory reaction of acute viral myocarditis induced by coxsackievirus B3 virus (CVB3) infection. METHODS: 100 male BALB/C mice were randomly divided into four groups, i.e. the normal control group, CVB3 group, CVB3 and bortezomib group, CVB3 and MG-132 group. Mice in control group were injected with blank solvent, while mice in other three groups were intraperitoneally inoculated with CVB3 to induce acute viral myocarditis. 24 h after infection, mice in treatment groups were administrated with bortezomib or MG-132 respectively for 7d continuously by intraperitoneal injection. Changes of myocardial ultra-structure, the mRNA and protein levels of IL-6 and TNF-α, the number of PMN, and the survival rate of each group were detected. RESULTS: Compared with control group, the protein levels of IL-6 and TNF-α, and the number of polymorphonuclear neutrophils (PMN) were significantly increased in CVB3 group (P<0.05). The cardiomyocytes were diffused and swelled, the myofilament was lysed, and the mitochondria was swelled and vacuolizated. The above mentioned inflammatory factors in bortezomib group and MG-132 group were significantly decreased as compared with CVB3 group (P<0.05). The damaged degree of the cardiomyocytes in treatment groups were less, and the mortality due to deadly arrhythmia were lower than that in CVB3 group. CONCLUSION: Proteasome inhibitors protect the mice from CVB3-induced acute viral myocarditis by suppressing the expression of inflammatory factors. Ubiquitin proteasome system is a potential new target therapy for viral myocarditis.

Key words: viral myocarditis, MG-132, inflammatory factor, PMN, IL-6, TNF-α

CLC Number:

R965.2

ZHANG Xinmin, CHEN Peng, YE Sheng, XIA Wujie, LI Yuechun. Proteasome inhibitors decrease IL-6 and TNF-α levels in mouse acute viral myocarditis[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(4): 406-411.

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