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Effects of thyroid hormone on macrophage dysfunction induced by oxidized low-density lipoprotein
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- Author:
- No author available
- Journal Title:
- Acta Physiologica Sinica
- Issue:
- 2
- DOI:
- 10.13294/j.aps.2018.0015
- Key Word:
- 甲状腺激素;氧化型低密度脂蛋白;巨噬细胞;甲状腺功能减退症;动脉粥样硬化
Abstract： 甲状腺功能减退症(甲减)患者的动脉粥样硬化(atherosclerosis,AS)及冠心病风险指数显著增加,但机制不清楚.巨噬细胞功能紊乱是促进AS斑块形成及发展的重要环节,本研究旨在探讨甲状腺激素对巨噬细胞功能的直接影响,为甲减相关AS的机制研究提供新思路.用氧化型低密度脂蛋白(oxidized low-density lipoprotein,oxLDL)诱导小鼠单核巨噬细胞系RAW264.7,建立体外巨噬泡沫细胞模型,并观察不同浓度甲状腺素(thyroxine,T4)对巨噬泡沫细胞功能的改善效应.分别采用MTT法、划痕实验、β-半乳糖苷酶染色实验检测巨噬细胞增殖、迁移功能及细胞衰老情况;ELISA法检测巨噬细胞分泌肿瘤坏死因子-α (tumor necrosis factor-α,TNF-α)、单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1)及白细胞介素-1β (interleukin-1β,IL-1β)情况;Western blot检测参与巨噬细胞增殖、迁移等过程的粘着斑激酶(focal adhesion kinase,FAK)的磷酸化水平.结果显示:oxLDL可显著抑制巨噬细胞增殖和迁移、促进其衰老及分泌TNF-α、MCP-1和IL-1β,而T4可浓度依赖性逆转oxLDL对巨噬细胞上述功能的影响;oxLDL可使巨噬细胞磷酸化FAK蛋白表达上调,而T4可浓度依赖性降低FAK蛋白磷酸化水平.上述结果提示,T4可呈浓度依赖性地调控巨噬细胞增殖、迁移、衰老及炎性因子分泌等功能.
- [1]熊怡淞,朱烨,陆慧琦,等.氧化型低密度脂蛋白对RAW264.7细胞Siglec-1表达及分泌细胞因子的影响[J].2010,(1).
- [2]E, Ortega,M J, Rodriguez,C, Barriga,etc.Corticosterone, prolactin and thyroid hormones as hormonal mediators of the stimulated phagocytic capacity of peritoneal macrophages after high-intensity exercise.[J].1996,17.
- [3]Perrotta,C.,Buldorini,M.,Assi,E.,etc.The thyroid hormone triiodothyronine controls macrophage maturation and functions: Protective role during inflammation[J].2014,184(1).
- [4]T P, Stossel.The machinery of cell crawling.[J].1994,271(3).
- [5]Lugli B,Rovida E,Giuntoli S,etc.Focal adhesion kinase is redistributed to focal complexes and mediates cell spreading in macrophages in response to M-CSF.[J].2005,386(9).
- [6]Harada, Takasuke,Yoshimura, Koichi,Yamashita, Osamu,etc.Focal Adhesion Kinase Promotes the Progression of Aortic Aneurysm by Modulating Macrophage Behavior[J].2017,37(1).
- [7]Zhang, Ming,Sara, Jaskanwal D. S.,Matsuzawa, Yasushi,etc.Clinical outcomes of patients with hypothyroidism undergoing percutaneous coronary intervention[J].2016,37(26).
- [8]Wang,P.,Xu,T.-Y.,Guan,Y.-F.,etc.Vascular smooth muscle cell apoptosis is an early trigger for hypothyroid atherosclerosis[J].2014,102(3).
- [9]Brandt,F.,Thvilum,M.,Brix,T.H.,etc.A review of the evidence for and against increased mortality in hypothyroidism[J].2012,8(7).
- [10]李红蓉,刘红利,马柳一.动脉粥样硬化进程中单核/巨噬细胞的行为变化[J].2015,(12).
- [11]Toshihiro, Ichiki.Thyroid Hormone and Vascular Remodeling.[J].2016.
- [12]Garcia JJ,Rodriguez AB,Ortega E,etc.Enhanced chemotaxis of macrophages by strenuous exercise in trained mice: thyroid hormones as possible mediators.[J].1999,201(1).
- [13]Tabas, Ira,Bornfeldt, Karin E..Macrophage Phenotype and Function in Different Stages of Atherosclerosis[J].2016,118(4).
- [14]Park YM,Febbraio M,Silverstein RL.CD36 modulates migration of mouse and human macrophages in response to oxidized LDL and may contribute to macrophage trapping in the arterial intima.[J].2009,119(1).
- [15]Martin KH,Slack JK,Weed SA,etc.Focal adhesion kinase: a regulator of focal adhesion dynamics and cell movement.[J].2000,19(49).
- [16]Mon, Naing Naing,Senga, Takeshi,Ito, Satoko.Interleukin-1 beta activates focal adhesion kinase and Src to induce matrix metalloproteinase-9 production and invasion of MCF-7 breast cancer cells[J].2017,13(2).
- [17]Zhao J,Guan JL.Signal transduction by focal adhesion kinase in cancer.[J].2009,28(1).
- [18]L F, Rosa,D A, Safi,R, Curi.Effect of hypo- and hyperthyroidism on the function and metabolism of macrophages in rats.[J].1995,13(2).
- [19]Ichiki,T..Thyroid hormone and atherosclerosis[J].2010,52(3).
- [20]M A, Forner,C, Barriga,E, Ortega.Exercise-induced stimulation of murine macrophage phagocytosis may be mediated by thyroxine.[J].1996,80(3).
- [21]A E,Hak.Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study.[J].2000,132.
- [22]H. Huang,P. Koelle,M. Fendler,etc.Induction of inducible nitric oxide synthase (iNOS) expression by oxLDL inhibits macrophage derived foam cell migration[J].2014,235(1).
- [23]Lan Haibing,Wang Xiaojing,Wang Nan,etc.Macrophage migration inhibitory factor (MIF) promotes rat airway muscle cell proliferation and migration mediated by ERK1/2 and FAK signaling[J].2018,42(1).
- [24]Reichardt LF,Gerald W,Pylayeva Y,etc.Ras- and PI3K-dependent breast tumorigenesis in mice and humans requires focal adhesion kinase signaling.[J].2009,119(2).
- [25]Billon, Cyrielle,Canaple, Laurence,Fleury, Sebastien,etc.TR alpha Protects Against Atherosclerosis in Male Mice: Identification of a Novel Anti-Inflammatory Property for TR alpha in Mice[J].2014,155(7).
- [26]Lan, Linxiang,Holland, Jane D.,Qi, Jingjing,etc.Shp2 signaling suppresses senescence in PyMT-induced mammary gland cancer in mice[J].2015,34(11).