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川崎病晚期患儿血清诱导THP-1巨噬细胞中MCP1、CCR2和iNOS表达

Induction of MCP1, CCR2, and iNOS expression in THP-1 macrophages by serum of children late after Kawasaki disease.

作者信息

Cheung Yiu-Fai, O Karmin, Tam Sidney C F, Siow Yaw L

机构信息

Department of Paediatrics and Adolescent Medicine, Grantham Hospital, The University of Hong Kong, China.

出版信息

Pediatr Res. 2005 Dec;58(6):1306-10. doi: 10.1203/01.pdr.0000183360.79872.1c.

Abstract

Evidence of premature atherosclerosis late after Kawasaki disease (KD) is accumulating. Given the potential roles of monocyte chemoattractant protein-1 (MCP-1), chemokine receptor CCR-2, and inducible nitric oxide synthase (iNOS) in atherogenesis, we sought to determine whether serum obtained from children late after KD would induce expression of these genes in macrophages in vitro. A total of 79 subjects were studied, which comprised 57 KD patients, 33 of whom had coronary aneurysms, and 22 age-matched controls. Expression of MCP-1, CCR2, and iNOS mRNA in THP-1 macrophages in the presence of patient and control serum was quantified as a ratio to beta-actin mRNA and expressed as a percentage of control. MCP-1 expression was significantly increased in the presence of serum from patients with coronary aneurysms. Expression of CCR2 and iNOS was significantly increased when THP-1 macrophages were incubated with serum from patients with and without coronary aneurysms. The magnitude of induction of MCP-1, CCR2, and iNOS or in combinations correlated positively with serum high-sensitivity C-reactive protein (hs-CRP), and low-density lipoprotein (LDL) cholesterol levels and negatively with high-density lipoprotein (HDL) cholesterol level. In conclusion, the serum of patients with a history of KD induces expression of MCP-1, CCR2, and iNOS in THP-1 macrophages in vitro. Induction of these genes in vivo may be related to chronic inflammation and may have important implications for premature atherosclerosis.

摘要

川崎病(KD)后晚期出现动脉粥样硬化过早的证据正在不断积累。鉴于单核细胞趋化蛋白-1(MCP-1)、趋化因子受体CCR-2和诱导型一氧化氮合酶(iNOS)在动脉粥样硬化形成中的潜在作用,我们试图确定KD患儿晚期的血清是否会在体外诱导巨噬细胞中这些基因的表达。共研究了79名受试者,其中包括57名KD患者,其中33名患有冠状动脉瘤,以及22名年龄匹配的对照者。在存在患者血清和对照血清的情况下,THP-1巨噬细胞中MCP-1、CCR2和iNOS mRNA的表达量与β-肌动蛋白mRNA的量进行定量比较,并以对照的百分比表示。在存在冠状动脉瘤患者血清的情况下,MCP-1表达显著增加。当THP-1巨噬细胞与有或无冠状动脉瘤患者的血清孵育时,CCR2和iNOS的表达显著增加。MCP-1、CCR2和iNOS单独或联合诱导的程度与血清高敏C反应蛋白(hs-CRP)、低密度脂蛋白(LDL)胆固醇水平呈正相关,与高密度脂蛋白(HDL)胆固醇水平呈负相关。总之,有KD病史患者的血清在体外可诱导THP-1巨噬细胞中MCP-1、CCR2和iNOS的表达。这些基因在体内的诱导可能与慢性炎症有关,并且可能对过早发生的动脉粥样硬化具有重要意义。

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