巨噬细胞极化
炎症
环氧化物水解酶2
脂肪组织
脂多糖
脂肪组织巨噬细胞
M2巨噬细胞
卵清蛋白
化学
肿瘤坏死因子α
内科学
内分泌学
免疫学
巨噬细胞
医学
药理学
白色脂肪组织
生物化学
免疫系统
酶
体外
作者
Xiaofeng Lin,Yuanyuan Zhang,Xinyu Zhou,Chuqiao Lai,Yaoyao Dong,Weixi Zhang
标识
DOI:10.1016/j.bcp.2023.115948
摘要
Obesityincreasestheriskofasthma and tends to enhance the asthma severity, however, its mechanism is not fully elucidated. The expansion of adipose tissue in obesity is accompanied by the accumulation of adiposetissue macrophages (ATMs) that could contribute to alow-gradeinflammationstate. In this study, we researched the regulatory role of soluble epoxide hydrolase (sEH) on ATMs-mediated inflammation in obese asthma. A mouse model of obese asthma that induced by high-fat diet (HFD) feeding and Ovalbumin (OVA) sensitization was employed to investigate the effects of AUDA, a sEH inhibitor (sEHi), on airway inflammation, airway hyperresponsivenesss (AHR) and pulmonary pathological changes. In addition to alleviating the key features of asthma in obese mice, we confirmed that AUDA reduced the expression of pro-inflammatory factor, such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumornecrosisfactor-α (TNF-α) in adipose tissue and serum. Moreover, AUDA could remarkedly reduce Lipopolysaccharide (LPS)-elevated IL-1β, IL-6 and TNF-α in RAW264.7 macrophage cells. Mechanistically, AUDA effectively reduced inflammation in adipose tissue, resulting in reduced systemic inflammation, by inhibiting M1-type macrophage polarization and promoting M2-type macrophage polarization. These processes were found to act through ERK1/2 signaling pathway. Herein, we proved that inhibition of sEH expression helped to mitigate multiple parameters of obese asthma by regulating the balance of M1/M2 macrophage polarization in adipose tissue.
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