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内脂素-1 通过抑制 TLR4/MyD88/NF-κB 信号通路来减轻脂多糖(LPS)诱导的 U937 巨噬细胞的激活。

Omentin-1 attenuates lipopolysaccharide (LPS)-induced U937 macrophages activation by inhibiting the TLR4/MyD88/NF-κB signaling.

机构信息

Department of Critical Care Medicine, The Second Affiliated Hospital of Hainan Medical University, Haikou City, Hainan province, China.

Department of Infectious Disease, The Affiliated Hainan Hospital of Hainan Medical University, Haikou City, Hainan province, China.

出版信息

Arch Biochem Biophys. 2020 Jan 15;679:108187. doi: 10.1016/j.abb.2019.108187. Epub 2019 Nov 9.

DOI:10.1016/j.abb.2019.108187
PMID:31706880
Abstract

Macrophages play a pivotal role in the defense response against harmful pathogens and stimuli by releasing various pro-inflammatory mediators. However, overproduction of pro-inflammatory mediators will do harm to the organism and cause inflammation-associated diseases. Omentin-1, which is a newly discovered adipokine, is specifically expressed in omental adipose tissue. Recent studies have found correlations between omentin-1 and insulin resistance, diabetes, obesity, inflammation, atherosclerosis, bone metabolism, and tumor cell proliferation. Some studies have shown that the association between omentin-1, insulin resistance, and inflammation might suggest that omentin-1 plays an important role in chronic inflammatory diseases. In this study, we found that omentin-1 inhibited LPS-induced expression of inflammatory mediators and pro-inflammatory cytokines in macrophages. Furthermore, omentin-1 inhibited activation of the NF-κB pathway by suppressing both nuclear p65 accumulation and transfected NFκB promoter activity. Importantly, omentin-1 increased nuclear translocation of Nrf2. Our findings demonstrate that omentin-1 exerts anti-inflammatory effects on LPS-induced macrophages and has potential implication in the treatment of inflammation-associated diseases.

摘要

巨噬细胞通过释放各种促炎介质在防御反应中发挥关键作用,以对抗有害病原体和刺激物。然而,促炎介质的过度产生会对机体造成伤害,并导致炎症相关疾病。网膜素-1 是一种新发现的脂肪因子,特异性表达于网膜脂肪组织。最近的研究发现网膜素-1与胰岛素抵抗、糖尿病、肥胖、炎症、动脉粥样硬化、骨代谢和肿瘤细胞增殖之间存在相关性。一些研究表明,网膜素-1、胰岛素抵抗和炎症之间的关联可能表明网膜素-1在慢性炎症性疾病中发挥重要作用。在本研究中,我们发现网膜素-1可抑制 LPS 诱导的巨噬细胞中炎症介质和促炎细胞因子的表达。此外,网膜素-1通过抑制核 p65 积累和转染 NFκB 启动子活性来抑制 NF-κB 途径的激活。重要的是,网膜素-1增加了 Nrf2 的核易位。我们的研究结果表明,网膜素-1对 LPS 诱导的巨噬细胞发挥抗炎作用,可能对炎症相关疾病的治疗具有潜在意义。

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