title: Interleukin-37 ameliorates myocardial ischaemia/reperfusion injury in mice.
abstract: 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.
authors: The Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: B
authors: B
authors: Wu
authors: K
authors: K
authors: Meng
authors: Q
authors: Q
authors: Ji
authors: M
authors: M
authors: Cheng
authors: K
authors: K
authors: Yu
authors: X
authors: X
authors: Zhao
authors: H
authors: H
authors: Tony
authors: Y
authors: Y
authors: Liu
authors: Y
authors: Y
authors: Zhou
authors: C
authors: C
authors: Chang
authors: Y
authors: Y
authors: Zhong
authors: Z
authors: Z
authors: Zhu
authors: W
authors: W
authors: Zhang
authors: X
authors: X
authors: Mao
authors: Q
authors: Q
authors: Zeng
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D016753:Interleukin-10 / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D016207:Cytokines; C508587:IL37 protein, human; D007375:Interleukin-1; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D016753:Interleukin-10
keywords: I/R injury; IL-37; ROS; TLR-4/NF-κB; apoptosis