Effect of emodin on the expression of TLR 4 and P 38 MAPK in mouse cardiac tissues with viral myocarditis

Toll-like receptor 4 (TLR4) and P38 mitogen activating protein kinase (P38MAPK) play important roles in pathogenesis of viral myocarditis (VMC). This study established a mouse VMC model, on which the dynamic expression level of TLR4 and P38MAPK was observed, along with the effect of emodin and its potential mechanism of cardiac protection. A total of 90 male BALB/c mice were randomly assigned into control, model and emodin groups (N=30 each). Coxsackie virus B3 (CVB3) was injected peritoneally to establish VMC model. 3 mg/kg/d emodin was given by gavage for 14 days. The mortality rate of mice was recorded. Viral titer was determined at day 7 by sacrificing 5 mice from each group. Fluorescent quantitative PCR was used to quantify mRNA copy number of CVB3. Eight animals were selected at day 7 and day 14 from each group to observe the cardiac morphology by H&E staining. RTPCR was used to detect TLR4 mRNA, while P38MAPK expression was measured by Western blotting. Model group had significantly elevated expression of P38MAPK and TLR4 mRNA levels compared to control group (P<0.05). Emodin treatment significantly decreased mortality rate, viral titer, copy number of CVB3 mRNA, cardiac pathology score, and mRNA expression of P38MAPK and TLR4 in heart tissues (P<0.05). During pathogenesis of VMC, TLR4 and P38MAPK signal transduction pathways may exert important roles. Emodin may alleviate cardiac injury of CVB3-infected mice via depressing TL4 and P38MAPK expression, thus protecting cardiac tissues.

[1]  C. Garlanda,et al.  The immunoproteasome controls the availability of the cardioprotective pattern recognition molecule Pentraxin3 , 2016, European journal of immunology.

[2]  Bingren Gao,et al.  Argonaute proteins in cardiac tissue contribute to the heart injury during viral myocarditis. , 2016, Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology.

[3]  Paul J. Hanson,et al.  Emodin inhibits coxsackievirus B3 replication via multiple signalling cascades leading to suppression of translation. , 2016, The Biochemical journal.

[4]  Juan Song,et al.  Gene expression analysis during recovery process indicates the mechanism for innate immune injury and repair from Coxsackievirus B3-induced myocarditis. , 2016, Virus research.

[5]  Lixiang Luo,et al.  Recombinant Mouse β-Defensin 3 Protects against Coxsackievirus B3-Induced Myocarditis in Mice , 2016, Intervirology.

[6]  B. Pieske,et al.  Update on Myocarditis and Inflammatory Cardiomyopathy: Reemergence of Endomyocardial Biopsy. , 2016, Revista espanola de cardiologia.

[7]  Li Yue-chun,et al.  Autonomic Nervous System in Viral Myocarditis: Pathophysiology and Therapy. , 2016, Current pharmaceutical design.

[8]  X. Ye,et al.  Cleavage of DAP5 by coxsackievirus B3 2A protease facilitates viral replication and enhances apoptosis by altering translation of IRES-containing genes , 2015, Cell Death and Differentiation.

[9]  Ping-guo Liu,et al.  Interleukin-27 ameliorates coxsackievirus-B3-induced viral myocarditis by inhibiting Th17 cells , 2015, Virology Journal.

[10]  Chunxiang Zhang,et al.  Panax Notoginseng Saponins Ameliorates Coxsackievirus B3-Induced Myocarditis by Activating the Cystathionine-γ-Lyase/Hydrogen Sulfide Pathway , 2015, Journal of Cardiovascular Translational Research.

[11]  Shaodong Guo,et al.  Activation of AMPK restricts coxsackievirus B3 replication by inhibiting lipid accumulation. , 2015, Journal of molecular and cellular cardiology.

[12]  Wen-jun Liu,et al.  Coxsackievirus B3 induces viral myocarditis by upregulating toll-like receptor 4 expression , 2015, Biochemistry (Moscow).

[13]  Hua Peng,et al.  GYY4137, a hydrogen sulfide‑releasing molecule, inhibits the inflammatory response by suppressing the activation of nuclear factor‑kappa B and mitogen‑activated protein kinases in Coxsackie virus B3‑infected rat cardiomyocytes. , 2015, Molecular medicine reports.

[14]  G. V. Chaitanya,et al.  Distinct kinetics of viral replication, T cell infiltration, and fibrosis in three phases of myocarditis following Theiler's virus infection. , 2014, Cellular immunology.

[15]  J. Francis,et al.  Central blockade of TLR4 improves cardiac function and attenuates myocardial inflammation in angiotensin II-induced hypertension. , 2014, Cardiovascular research.

[16]  N. Mackman,et al.  Multiple roles of the coagulation protease cascade during virus infection. , 2014, Blood.

[17]  S. Huber,et al.  Sex differences in TLR2 and TLR4 expression and their effect on coxsackievirus-induced autoimmune myocarditis. , 2013, Experimental and molecular pathology.

[18]  Qinghua Zhang,et al.  MicroRNAs Regulate the Pathogenesis of CVB3-Induced Viral Myocarditis , 2012, Intervirology.

[19]  M. Opavsky,et al.  The coxsackie-adenovirus receptor induces an inflammatory cardiomyopathy independent of viral infection. , 2011, Journal of molecular and cellular cardiology.

[20]  Yuanyuan Ding,et al.  Influence of Cinnamaldehyde on Viral Myocarditis in Mice , 2010, The American journal of the medical sciences.

[21]  Ying-zhen Yang,et al.  Pathogenesis of coxsackievirus B3-induced myocarditis: role of macrophage migration inhibitory factor. , 2012, Chinese medical journal.