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Exogenous IL-19 Attenuates Acute Ischaemic Injury and Improves Survival in Male Mice With Myocardial Infarction

Exogenous IL-19 Attenuates Acute Ischaemic Injury and Improves Survival in Male Mice With Myocardial Infarction

Weishuai An, Yongsheng Yu, Yuefan Zhang, Zhigang Zhang, Yunhua Yu, Xianxian Zhao

Br J Pharmacol. 2019 Mar;176(5):699-710.

PMID: 30460984

Abstract:

Background and purpose:
Myocardial infarction (MI) is one of the leading causes of death in China and often results in the development of heart failure. In this work, we tested the therapeutic role of Interleukin-19 (IL-19) in mice with MI and investigated the underlying molecular mechanism.
Experimental approach:
Mice were subjected to MI by ligation of left anterior descending coronary artery (LAD) and treated with IL-19 (10ng g-1 ; i.p.).
Key results:
Protein expression of IL-19 and its receptor in myocardium were upregulated 24 hrs post-MI in male mice. IL-19 treatment decreased infarct and apoptosis in myocardium, accompanied by enhanced haem oxygenase-1 (HO-1) activities and reduced malondialdehyde (MDA) formation. Pretreatment with IL-19 upregulated HO-1 expression in cultured neonatal mouse ventricular myocytes and attenuated oxygen-glucose deprivation (OGD)-induced injuries in vitro. Furthermore, IL-19 preserved cardiac function and improved survival of mice with MI. IL-19 reduced inflammatory infiltrates and suppressed formation of TNF-α, IL-1β, and IL-6. More importantly, IL-19 inhibited polarization toward proinflammatory M1 macrophages and stimulated M2 macrophage polarization in myocardium of mice with MI. IL-19 enhanced protein levels of vascular endothelial growth factor (VEGF) and promoted angiogenesis in myocardium of mice with MI. In addition, IL-19 treatment increased DNA-binding of the transcription factor STAT3 in myocardium of mice with MI.
Conclusions and implications:
Treatment with exogenous IL-19 attenuated acute ischemic injury and improved survival of mice with MI. The mechanisms underlying these effects involved induction of HO-1, M2 macrophage polarization, angiogenesis, and STAT3 activation.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413373	IL-19 from mouse			Price

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