MAPK1敲低可改善难治性哮喘小鼠模型的免疫和炎症异常

IF 0.6 4区 医学 Q4 PHARMACOLOGY & PHARMACY
Shuang Lin, Xiaohong Yang
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引用次数: 0

摘要

目的:在动物模型中评估难治性哮喘的潜在分子机制,以及MAPK1敲低对该疾病的潜在治疗作用。方法:8 ~ 10周龄的ICR雌性小鼠18只,随机分为对照组、哮喘模型组和难治性哮喘组,每组6只。使用腺病毒载体敲低MAPK1在小鼠中的表达。随后,使用甲基化测定法测定小鼠肺组织中MAPK1启动子的甲基化水平。采用苏木精和伊红(H&E)染色和周期性酸-希夫(PAS)染色检测肺组织的炎症和组织学变化。流式细胞术检测免疫细胞水平,Western blotting检测ERK1/2、JNK、MEK1/2、p38蛋白表达水平。结果:甲基化分析结果显示,在难治性哮喘小鼠模型中,cg11335969位点的平均甲基化水平显著降低(p <0.05)。MAPK1敲低后,难治性哮喘小鼠IgG1和IgM水平降低。小鼠肺部病变程度显著降低(p <0.05),有效降低了组织病理变化。ERK1/2、JNK、MEK1/2和p38蛋白水平以及中性粒细胞、树突状细胞和巨噬细胞水平显著降低(p <0.05)。结论:难治性哮喘小鼠模型中存在MAPK1 cg11335969位点的高甲基化修饰。在难治性哮喘小鼠中,敲低MAPK1可减轻炎症和组织损伤,逆转异常免疫细胞数量。因此,抑制MAPK1可能是改善难治性哮喘免疫异常的新策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
MAPK1 knockdown ameliorated immune and inflammatory abnormalities in a mouse model of refractory asthma
Purpose: To evaluate the potential molecular mechanisms involved in refractory asthma in an animal model, and the potential therapeutic effect of MAPK1 knockdown on the disease.Methods: Eighteen female Institute of Cancer Research (ICR) mice, aged 8 - 10 weeks, were randomly divided into three groups: control, asthma model and refractory asthma, with 6 mice in each group. The expression of MAPK1 was knocked down in mice using an adenoviral vector. Subsequently, the methylation levels of MAPK1 promoter in mouse lung tissue were determined using methylation assays. Hematoxylin and eosin (H&E) staining and Periodic Acid-Schiff (PAS) staining were used to determine inflammatory and histological changes in lung tissues. Levels of immune cells were determined using flow cytometry, while Western blotting was used to measure the protein expression levels of ERK1/2, JNK, MEK1/2 and p38.Results: Methylation assay results show that mean methylation level of cg11335969 locus was significantly reduced in the refractory asthma mouse model (p < 0.05). The levels of IgG1 and IgM in refractory asthmatic mice were reduced after MAPK1 knockdown. There was a significantly reduced degree of lung lesions in mice (p < 0.05), as was reflected in effectively decreased histopathological changes. Protein levels of ERK1/2, JNK, MEK1/2 and p38, and the levels of neutrophils, dendritic cells, and macrophages were significantly decreased (p < 0.05).Conclusion: There is hypermethylated modification of MAPK1 at cg11335969 site in refractory asthma mouse model. Knockdown of MAPK1 attenuates inflammation and tissue damage, and reverses abnormal immune cell numbers in refractory asthma mice. Thus, MAPK1 inhibition may be a novel strategy for ameliorating immune abnormalities in refractory asthma.
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来源期刊
CiteScore
1.00
自引率
33.30%
发文量
490
审稿时长
4-8 weeks
期刊介绍: We seek to encourage pharmaceutical and allied research of tropical and international relevance and to foster multidisciplinary research and collaboration among scientists, the pharmaceutical industry and the healthcare professionals. We publish articles in pharmaceutical sciences and related disciplines (including biotechnology, cell and molecular biology, drug utilization including adverse drug events, medical and other life sciences, and related engineering fields). Although primarily devoted to original research papers, we welcome reviews on current topics of special interest and relevance.
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