SummaryInnate 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.

No abstract

Accumulating evidences suggest that longnon-coding RNAs (lncRNAs) play functional roles in development of different cancers, including cancer initiation and progression. Metastasis associated lung adenocarcinoma transcript 1(MALAT1) is a well-known lncRNA which was previously shown to be a direct target of miR-125b in bladder cancer (BCa) and to promote cancer progression and invasion. However, little is known whether MALAT1 can also target miR-125b. In the present study, using CRISPR-based technologies and qRT-PCR, we show that MALAT1 is capable of suppressing mature miR-125b and increasing the expression of its target genes (Bcl-2 and MMP-13), but has no effect on pri-miR-125b and pre-miR-125b. We observe that the biotin-labeled MALAT1-RNA probe is able to pull down Ago2 and miR-125b and that the negative regulation of miR-125b by MALAT1 is dependent on Ago2. Importantly, the results of flow cytometry assay and transwell assay reveal that the MALAT1-mediated cancer progression is in part due to specific suppression of miR-125b and activation of its two target genes. All together, these data suggest that the “MALAT1-miR-125b-Bcl-2 / MMP-13” axis plays an important role in the progression of BCa, thereby may provide a potential therapeutic strategy for the treatment of human BCa.

BackgroundExcessive immune‐mediated inflammatory reactions play a deleterious role in postinfarction ventricular remodeling. Interleukin‐37 (IL‐37) emerges as an inhibitor of both innate and adaptive immunity. However, the exact role of IL‐37 and IL‐37 plus troponin I (TnI)–treated dendritic cells (DCs) in ventricular remodeling after myocardial infarction (MI) remains elusive.Methods and Results MI was induced by permanent ligation of the left anterior descending artery. Our results showed that treatment with recombinant human IL‐37 significantly ameliorated ventricular remodeling after MI, as demonstrated by decreased infarct size, better cardiac function, lower mortality, restricted inflammatory responses, decreased myocardial fibrosis, and inhibited cardiomyocyte apoptosis. In vitro, we examined the phenotype of IL‐37 plus TnI–conditioned DCs of male C57BL/6 mice and their capacity to influence the number of regulatory T cells. Our results revealed that IL‐37 plus TnI–conditioned DCs obtained the characteristics of tolerogenic DCs (tDCs) and expanded the number of regulatory T cells when co‐cultured with splenic CD4+ T cells. Interestingly, we also found that adoptive transfer of these antigen‐loaded tDCs markedly increased the number of regulatory T cells in the spleen, attenuated the infiltration of inflammatory cells in the infarct hearts, decreased myocardial fibrosis, and improved cardiac function.ConclusionsOur results reveal a beneficial role of IL‐37 or tDCs treated with IL‐37 plus TnI in post‐MI remodeling that is possibly mediated by reestablishing a tolerogenic immune response, indicating that IL‐37 or adoptive transfer of IL‐37 plus TnI–treated tDCs may be a novel therapeutic strategy for ventricular remodeling after MI.