Interleukin-37 ameliorates myocardial ischaemia/reperfusion injury in mice
Interleukin-37 ameliorates myocardial ischaemia/reperfusion injury in mice
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Interleukin-37 可改善小鼠心肌缺血/再灌注损伤。
DOI：
10.1111/cei.12284
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发表时间：
2014-06-01
影响因子：
4.6
通讯作者：
Zeng, Q.
中科院分区：
文献类型：
--
作者：
Wu, B.;Meng, K.;Zeng, Q.
先天免疫和炎症反应参与了心肌缺血/再灌注损伤。白介素37是新近发现的白介素1家族成员，是天然免疫和炎症的基本抑制因子。然而，它在心肌I/R损伤中的作用仍不清楚。对雄性C57BL/6J小鼠进行I/R或假手术。I/R小鼠在再灌流前立即注射重组人IL-37或赋形剂。与赋形剂治疗组相比，IL-37治疗组小鼠心肌I/R损伤明显改善，表现为心肌梗死面积缩小，心肌肌钙蛋白T水平降低，心功能改善。这种保护作用与IL-37抑制促炎细胞因子、趋化因子的产生和中性粒细胞的浸润有关，这些因素共同导致心肌细胞凋亡和活性氧(ROS)的产生减少。此外，我们还发现IL-37抑制了I/R后Toll样受体(TLR)-4的表达上调和核因子-kB(NF-kB)的激活，同时提高了抗炎IL-10的水平。此外，给予抗IL-10R抗体可阻断IL-37对I/R损伤的保护作用。体外实验进一步证明，IL-37对I/R状态下的心肌细胞具有保护作用，并抑制中性粒细胞向趋化因子Lix的迁移能力。综上所述，IL-37对小鼠心肌I/R损伤具有保护作用，为心肌I/R损伤提供了一种有前景的治疗介质。
Innate immune and inflammatory responses are involved in myocardial ischaemia/reperfusion (I/R) injury. Interleukin (IL)-37 is a newly identified member of the IL-1 family, and functions as a fundamental inhibitor of innate immunity and inflammation. However, its role in myocardial I/R injury remains unknown. I/R or sham operations were performed on male C57BL/6J mice. I/R mice received an injection of recombinant human IL-37 or vehicle, immediately before reperfusion. Compared with vehicle treatment, mice treated with IL-37 showed an obvious amelioration of the I/R injury, as demonstrated by reduced infarct size, decreased cardiac troponin T level and improved cardiac function. This protective effect was associated with the ability of IL-37 to suppress production of proinflammatory cytokines, chemokines and neutrophil infiltration, which together contributed to a decrease in cardiomyocyte apoptosis and reactive oxygen species (ROS) generation. In addition, we found that IL-37 inhibited the up-regulation of Toll-like receptor (TLR)-4 expression and nuclear factor kappa B (NF-kB) activation after I/R, while increasing the anti-inflammatory IL-10 level. Moreover, the administration of anti-IL-10R antibody abolished the protective effects of IL-37 in I/R injury. In-vitro experiments further demonstrated that IL-37 protected cardiomyocytes from apoptosis under I/R condition, and suppressed the migration ability of neutrophils towards the chemokine LIX. In conclusion, IL-37 plays a protective role against mouse myocardial I/R injury, offering a promising therapeutic medium for myocardial I/R injury.