期刊
MOLECULAR IMMUNOLOGY
卷 48, 期 4, 页码 706-713出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2010.11.018
关键词
CVB3; Myocarditis; CCL2; Gene therapy; Inflammation
资金
- China NSFC [81072413]
- Jiangsu Pan-Deng Project [BK2010004]
- National Science and Technology [2009ZX10004-104]
- Major State Basic Research Development Program of China [2007CB512401]
- Program for Outstanding Medical Academic Leader [LJ06011]
Viral myocarditis, which is most prevalently caused by Coxsackievirus B3 (CVB3) infection, affects about 5-20% of the world population and lacks efficient treatments. We previously reported that monocyte chemotactic protein-1 (MCP-1, CCL2) was significantly induced during CVB3 infection and greatly contributed to the myocardic inflammation and injury. Herein a CCL2 mutant with removed chemotactic activity was administrated and its therapeutic effect on CVB3-induced myocarditis was explored. A dominant negative CCL2 mutant, lacking the N-terminal amino acids 2-8 (CCL2(Delta 2-8)), was genetically constructed and intramuscularly injected into BALB/c mice after CVB3 infection, severity of myocarditis was evaluated by weight loss, survival rate, serological indices and pathological observation. Systemic and local Th1 /Th2 cytokine profiles were also assessed. Mice receiving pCCL2(Delta 2-8) exhibited a profound attenuation of myocarditis compared to pcDNA3.1 or non-treated mice, as evidenced by invariant body weight, decreased serum CK-MB level, reduced myocardial inflammatory infiltration and increased survival. This effect was not attributable to the efficient viral clearance, but associated with weakened Th1 immune responses, as evidenced by significantly reduced CD4(+)IFN-gamma(+) T cell frequency and Th1 cytokine level systemically and locally. Strategy of blocking in vivo CCL2 activity could effectively alleviate the severity of CVB3-induced myocarditis and may present an alternative therapeutic approach against viral myocarditis. (C) 2010 Elsevier Ltd. All rights reserved.
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