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Objective: Nuclear factor kappa-B (NF-κB)-induced inflammation leads to myocarditis and heart dysfunction. How microRNAs (miRNAs) contribute to this process is poorly defined. The aim of this study was to investigate whether miRNAs regulate NF-κB-induced inflammation in experimental autoimmune myocarditis (EAM) in vivo. Methods and Results: NF-κB and its related proinflammatory genes, including interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a), were activated in EAM. Profiling of NF-κB-related miRNAs revealed that miR-590-3p was strikingly reduced in EAM. We found IL-6-induced proinflammatory signaling via miR-590-3p reduction, p50 induction, NF-κB activation and IL-6/TNF-a expression. Moreover, a luciferase reporter assay demonstrated that miR-590-3p directly interacted with the 3' UTR (untranslated region) of the p50 subunit, and that miR-590-3p overexpression inhibited p50 expression. Finally, miR-590-3p transfection through adeno-associated virus significantly inhibited p50 expression, suppressed NF-κB activity and blocked IL-6/TNF-a expression in vivo, reducing the lesion area and improving cardiac function in EAM. Conclusion: miR-590-3p is a novel NF-κB-related miRNA that directly targets the p50 subunit. This may provide a novel strategy for the treatment of myocarditis.

Purpose Pu-erh tea has recently become very popular in China and most southeast Asian countries. Fermented Pu-erh tea may help regulate blood lipids, prevent and treat atherosclerosis (AS). Below, we discuss the effects of Pu-erh tea on AS. Methods Blood lipid levels, plaque size and composition, proinfl ammatory cytokines expression and NF-κB binding activity were determined in ApoE null mice that consumed Pu-erh tea for either eight or 16 weeks. RAW264.7 cells were treated with Pu-erh tea water extract in vitro. Results In vivo, there were no signifi cant differences in blood lipid levels between the tea consumption groups and controls. Among the ApoE null mice who consumed pu-erh tea for 16 weeks, the mean plaque area decreased by 18.66%, the mean ratios of oil red O positive regions decreased by 18.05%, the mean proportion of macrophages in the plaque decreased by 41.29% and the apoptotic macrophages in plaque increased 2.69-fold. NF-κB binding activity in peritoneal macrophages decreased by 75.55% and the relative mRNA expression levels of IL-6, IL-12 and TNFα in the vascular tissue decreased by 17.83%, 36.39% and 43.73%, respectively. In vitro, The treatment of RAW264.7 cells with pu-erh tea water extract found the expression of the P65 could be reduced, whereas IκBβ expression in the cells increased. Using EMSA to detect the binding activity of NF-kB, increasing treatment concentrations decreased the mean grey value signifi cantly and depending on the length of treatment time. With extended intervention time and increased tea water extract concentrations, the mRNA expression levels of IL-6 decreased. When RAW264.7 were treated with a certain concentration of pu-erh tea water extract, within the fi rst 24 h and with the extension of the intervention time, the proportion of apoptotic cells continued to increase, and within increased concentrations of pu-erh tea extract for 24 h, the proportion of apoptotic cells continued to rise. Pretreated with PMA, the proportion of positive apoptotic cells decreased with most points, with the lowest point at 62.16% decreased; pretreated with Bay11-7085, the proportion of positive apoptotic cells increased, reaching a high point of 23.39% increased. After adding different concentrations of pu-erh tea water extract, no changes in the RAW264.7 cells' migration ability was observed. Pu-erh Tea water extract had no effect on macrophage foam cell formation, cholesterol concentration and effl ux rate, mRNA expression of ABCA1, ABCG1 and CD36 of RAW264.7 cells. Conclusion Pu-erh tea is able to inhibit a chronic infl ammatory state of the body and local blood vessels (take the decrease of the expression of TNFα and IL-6 as a sign) and reduce the activity of NF-κB expression, thus promoting macrophage apoptosis in the plaque, reducing the number of macrophages in plaque, and the plaque area and lipid deposition, on 28 August 2018 by guest. Protected by copyright.