摘要:
Atherosclerotic lesions are characterized by the accumulation of abundant lipids and chronic inflammation. Previous researches have indicated that macrophage-derived lipoprotein lipase (LPL) promotes atherosclerosis progression by accelerating lipid accumulation and proinflammatory cytokine secretion. Although apelin-13 has been regarded as an atheroprotective factor, it remains unclear whether it can regulate the expression of LPL. The aim of this study was to explore the effects of apelin-13 on the expression of LPL and the underlying mechanism in THP-1 macrophage-derived foam cells. Apelin-13 significantly decreased cellular levels of total cholesterol, free cholesterol, and cholesterol ester at the concentrations of 10 and 100 nM. ELISA analysis confirmed that treatment with apelin-13 reduced pro-inflammatory cytokine secretion, such as interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α). It was also found that apelin-13 inhibited the expression of LPL as revealed by western blot and real-time PCR analyses. Bioinformatics analyses and dual-luciferase reporter assay indicated that miR-361-5p directly downregulated the expression of LPL by targeting the 3'UTR of LPL. In addition, apelin-13 + miR-361-5p mimic significantly downregulated the expression of LPL in cells. Finally, we demonstrated that apelin-13 downregulated the expression of LPL through activating the activity of PKCa. Taken together, our results showed that apelin-13 downregulated the expression of LPL via activating the APJ/PKCa/miR-361 -5p signaling pathway in THP-1 macrophage-derived foam cells, leading to inhibition of lipid accumulation and proinflammatory cytokine secretion. Therefore, our studies provide important new insight into the inhibition of lipid accumulation and pro-inflammatory cytokine secretion by apelin-13, and high-light appelin-13 as a promising therapeutic target in atherosclerosis.
作者机构:
[Tang, Dan; Ou, Weiwei; Wang, Deming; Chen, Quan; Wang, Jiazheng; Xiao, Ji] Univ South China, Affiliated Hosp 2, Dept Anesthesiol, Hengyang 421001, Peoples R China.;[Mo, Zhongcheng] Univ South China, Dept Histol & Embryol, Hengyang 421001, Peoples R China.;[Tang, Chaoke] Univ South China, Inst Cardiovasc Res, Life Sci Res Ctr, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Peoples R China.;[Peng, Liangyu] Univ South China, Affiliated Hosp 1, Dept Anesthesiol, Hengyang 421001, Peoples R China.
通讯机构:
[Wang, Deming; Peng, Liangyu] U;Univ South China, Affiliated Hosp 2, Dept Anesthesiol, Hengyang 421001, Peoples R China.;Univ South China, Affiliated Hosp 1, Dept Anesthesiol, Hengyang 421001, Peoples R China.
关键词:
liver X receptor;cytokine;mRNA decay;tristetraprolin;mitogen-activated protein kinase
摘要:
Liver X receptors (LXRs) have anti-inflammatory properties. Whether LXRs play a role in post-transcriptional control of inflammatory cytokine expression is not clear. Here, we firstly identified that the synthetic LXR agonist T0901317 promoted IL-1β, IL-6 and TNFa mRNA degradation. Moreover, T0901317 destabilized TNFa mRNA through its 3'-untranslated region. In addition, T0901317 increased the expression of tristetraprolin (TTP), while antagonizing TTP with siRNA abrogated T0901317-mediated inflammatory cytokine mRNA decay. Interestingly, T0901317 repressed LPS-induced phosphorylation of ERK1/2 and p38 mitogen-activated protein kinase (MAPK) in THP-1 macrophages. The evidence presented here confirms that LXR activation with T0901317 inhibits the phosphorylation of ERK1/2 and p38 MAPK, likely resulting in the increased expression of TTP and the decay of LPS-induce inflammatory cytokine mRNAs.
摘要:
目的 观察橘皮素对PC-12细胞β淀粉样蛋白(Aβ)水平的影响并探讨其可能的机制。方法不同浓度(0.1、1、10、100μmol/L)的橘皮素,作用不同时间(0 h、6 h、12 h、24 h、48 h)处理PC-12细胞后,采用ELISA检测细胞培养液Aβ40和Aβ42水平,Western blot检测PC-12细胞三磷酸腺苷结合盒转运体A1(ABCA1)蛋白水平,RT-PCR检测PC-12细胞ABCA1 m RNA水平。ABCA1 Si RNA抑制ABCA1蛋白表达。结果 10μmol/L及100μmol/L橘皮素组Aβ40和Aβ42水平显著下降,ABCA1蛋白水平明显增加,而所有组ABCA1 m RNA水平没有改变。使用100μmol/L橘皮素处理PC-12细胞,处理后ABCA1 m RNA表达与对照组比较差异无显著性,24 h及48 h组ABCA1水平显著增加,Aβ40和Aβ42水平显著下降。使用ABCA1 Si RNA抑制PC-12细胞ABCA1蛋白表达后,ABCA1 si RNA处理组与对照组比较,Aβ40和Aβ42水平显著增加。结论 橘皮素可通过增加ABCA1蛋白来降低PC-12细胞Aβ40和Aβ42水平。
摘要:
高密度脂蛋白(high density lipoprotein,HDL)是主要的血脂成分之一,具有抗动脉粥样硬化、抗炎症反应等多种功能。近年来,HDL对微生物感染的影响得到广泛关注和研究。研究发现,微生物感染能够导致炎症反应,引起甘油三脂、极低密度脂蛋白、低密度脂蛋白升高,高密度脂蛋白(high density lipoprotein,HDL)降低。细菌感染时,HDL与HDL相关脂蛋白结合并中和革兰氏阴性菌的脂多糖和革兰氏阳性菌的磷壁酸,抑制炎症反应发生。寄生虫感染过程中,apo L-1通过溶酶体溶胀作用杀死寄生虫。本文主要综述HDL对微生物感染的影响,以期为抑制微生物感染引起的炎症反应提供新思路,为治疗败血症、微生物感染引起的疾病提供新方法。