M1型巨噬细胞糖代谢重编程机制及其在炎症启动中的关键作用

doi:10.3969/j.issn.1004-616x.2019.01.015

癌变·畸变·突变 ›› 2019, Vol. 31 ›› Issue (1): 79-81,85.doi: 10.3969/j.issn.1004-616x.2019.01.015

M1型巨噬细胞糖代谢重编程机制及其在炎症启动中的关键作用

姜晓旭¹, 郑义鹏², 赵九洲², 李明哲², 朱敬朴², 王欣³, 李永奇¹, 海春旭³, 于卫华³

1. 空军军医大学第一附属医院综合诊疗科, 陕西西安 710030;
2. 空军军医大学学员旅, 陕西西安 710032;
3. 空军军医大学军事预防医学院毒理学教研室, 陕西西安 710032

收稿日期:2018-03-30 修回日期:2018-09-13 出版日期:2019-01-31 发布日期:2019-01-31
通讯作者: 海春旭,E-mail:cx-hai@fmmu.edu.cn;于卫华,E-mail:yuweihua1@fmmu.edu.cn E-mail:cx-hai@fmmu.edu.cn;yuweihua1@fmmu.edu.cn
作者简介:姜晓旭,E-mail:511390237@qq.com;郑义鹏,E-mail:liuzeyu1271@163.com。
基金资助:
陕西省自然科学基金项目（2016JM8024）；国家自然科学基金（31800706，81573126）

Received:2018-03-30 Revised:2018-09-13 Online:2019-01-31 Published:2019-01-31

摘要/Abstract

摘要： 巨噬细胞是机体主要的炎症效应细胞，不仅是机体对抗感染的重要武器，而且与临床上大多数疾病的发生发展密切相关。正常细胞以葡萄糖氧化磷酸化途径代谢产能，在缺氧环境下则以糖酵解途径为主。而肿瘤细胞在氧气充足条件下也通过糖酵解代谢产能，这就是经典的Warburg效应理论。研究表明，M1型极化巨噬细胞可发生与肿瘤细胞类似的糖代谢重编程，表现为有氧糖酵解增强和氧化磷酸化减弱，而阻断糖代谢重编程可有效抑制炎症反应。近年来，免疫和代谢相关性研究成为学术界关注热点，并催生了免疫代谢学的概念，其中巨噬细胞与代谢的关联性研究也取得了丰硕成果。本文重点阐述了M1型极化巨噬细胞糖代谢重编程的可能机制，并分析了它在炎症启动调控中的关键作用，以期为临床上炎症相关疾病防治提供新策略。

关键词: M1型巨噬细胞, 糖代谢重编程, 炎症反应, 糖酵解, 氧化磷酸化

中图分类号:

R364.5

姜晓旭, 郑义鹏, 赵九洲, 李明哲, 朱敬朴, 王欣, 李永奇, 海春旭, 于卫华. M1型巨噬细胞糖代谢重编程机制及其在炎症启动中的关键作用[J]. 癌变·畸变·突变, 2019, 31(1): 79-81,85.

参考文献

[1] 李康,郭强,王翠妮,等. M1和M2型巨噬细胞表型的比较分析[J]. 现代免疫学,2008,28(3):177-183.
[2] 周宪宾,姚成芳. 巨噬细胞M1/M2极化分型的研究进展[J]. 中国免疫学杂志,2012,28(10):957-960.
[3] SICA A,ERRENI M,ALLAVENA P,et al. Macrophage polarization in pathology[J]. Cell Mol Life Sci,2015,72(21):4111-4126.
[4] PARISI L,GINI E,BACI D,et al. Macrophage polarization in chronic inflammatory diseases:killers or builders?[J]. J Immunol Res,2018,2018:8917804.
[5] BIANCHI M E,MANFREDI A A. How macrophages ring the inflammation alarm[J]. Proc Natl Acad Sci USA,2014,111(8):2866-2867.
[6] BASHIR S,SHARMA Y,ELAHI A,et al. Macrophage polarization:the link between inflammation and related diseases[J]. Inflamm Res,2016,65(1):1-11.
[7] 焦健华,王鹏,李积彬,等. 恶性肿瘤有氧糖酵解关键酶研究进展[J]. 转化医学杂志,2013,2(6):361-365.
[8] 易梅,向波,李小玲,等. 代谢重编程:肿瘤的平衡之舞[J]. 中南大学学报(医学版),2013,38(11):1177-1187.
[9] HARD G C. Some biochemical aspects of the immune macrophage[J]. Br J Exp Pathol,1970,51(1):97-105.
[10] BRUNE B,DEHNE N,GROSSMANN N,et al. Redox control of inflammation in macrophages[J]. Antioxid Redox Signal,2013,19(6):595-637.
[11] YU W,ZHANG X,WU H,et al. HO-1 is essential for tetrahydroxystilbene glucoside mediated mitochondrial biogenesis and anti-inflammation process in LPS-treated RAW264.7 macrophages[J]. Oxid Med Cell Longev,2017,2017:1818575.
[12] 侯阿龙,王睿,王进平,等. 代谢重编程调控巨噬细胞活化及其在疾病中的作用[J]. 现代医药卫生,2016,32(17):2621-2623.
[13] TANNAHILL G M,CURTIS A M,ADAMIK J,et al. Succinate is an inflammatory signal that induces IL-1beta through HIF-1 alpha[J]. Nature,2013,496(7444):238-242.
[14] YANG L,XIE M,YANG M,et al. PKM2 regulates the Warburg effect and promotes HMGB1 release in sepsis[J]. Nat Commun,2014,5:4436.
[15] ABAIS J M,XIA M,ZHANG Y,et al. Redox regulation of NLRP3 inflammasomes:ROS as trigger or effector?[J]. Antioxid Redox Signal,2015,22(13):1111-1129.
[16] LANGSTON P K,SHIBATA M,HORNG T. Metabolism supports macrophage activation[J]. Front Immunol,2017,8:61.
[17] BUCK M D,O'SULLIVAN D,KLEIN G R,et al. Mitochondrial dynamics controls T cell fate through metabolic programming[J]. Cell,2016,166(1):63-76.
[18] CLEETER M W,COOPER J M,DARLEY-USMAR V M,et al. Reversible inhibition of cytochrome c oxidase,the terminal enzyme of the mitochondrial respiratory chain,by nitric oxide. Implications for neurodegenerative diseases[J]. FEBS Lett,1994,345(1):50-54.
[19] EVERTS B,AMIEL E,VAN DER WINDT G J,et al. Commitment to glycolysis sustains survival of NO-producing inflammatory dendritic cells[J]. Blood,2012,120(7):1422-1431.
[20] MASCANFRONI I D,TAKENAKA M C,YESTE A,et al. Metabolic control of type 1 regulatory T cell differentiation by AHR and HIF1-alpha[J]. Nat Med,2015,21(6):638-646.
[21] TAI T C,WONG-FAULL D C,CLAYCOMB R,et al. Hypoxic stress-induced changes in adrenergic function:role of HIF1 alpha[J]. J Neurochem,2009,109(2):513-524.
[22] MIYASAKA A,ODA K,IKEDA Y,et al. PI3K/mTOR pathway inhibition overcomes radioresistance via suppression of the HIF1-alpha/VEGF pathway in endometrial cancer[J]. Gynecol Oncol,2015,138(1):174-180.
[23] ZEPEDA A B,PESSOA A J,CASTILLO R L,et al. Cellular and molecular mechanisms in the hypoxic tissue:role of HIF-1 and ROS[J]. Cell Biochem Funct,2013,31(6):451-459.
[24] BRAVERMAN J,STANLEY S A. Nitric oxide modulates macrophage responses to mycobacterium tuberculosis infection through activation of HIF-1alpha and repression of NF-kappa B[J]. J Immunol,2017,199(5):1805-1816.
[25] 韩孝先,刘泽宇,周庆彪,等. 线粒体在炎症调控中的作用研究进展[J]. 癌变·畸变·突变,2017,29(6):467-470.
[26] CORCORAN S E,O'NEILL L A. HIF1alpha and metabolic reprogramming in inflammation[J]. J Clin Invest,2016,126(10):3699-3707.
[27] TSCHOPP J. Mitochondria:Sovereign of inflammation?[J]. Eur J Immunol,2011,41(5):1196-1202.
[28] RAMBOLD A S,PEARCE E L. Mitochondrial dynamics at the interface of immune cell metabolism and function[J]. Trends Immunol,2018,39(1):6-18.
[29] MANCINI S J,SALT I P. Investigating the role of AMPK in inflammation[J]. Methods Mol Biol,2018,1732:307-319.
[30] LIN D S,KAO S H,HO C S,et al. Inflexibility of AMPK-mediated metabolic reprogramming in mitochondrial disease[J]. Oncotarget,2017,8(43):73627-73639.
[31] SHIMIZU Y,POLAVARAPU R,ESKLA K L,et al. Hydrogen sulfide regulates cardiac mitochondrial biogenesis via the activation of AMPK[J]. J Mol Cell Cardiol,2018,116:29-40.
[32] MOREIRA D,RODRIGUES V,ABENGOZAR M,et al. Leishmania infantum modulates host macrophage mitochondrial metabolism by hijacking the SIRT1-AMPK axis[J]. PLoS Pathog,2015,11(3):e1004684.
[33] MENG Z,JING H,GAN L,et al. Resveratrol attenuated estrogen-deficient-induced cardiac dysfunction:role of AMPK,SIRT1,and mitochondrial function[J]. Am J Transl Res,2016,8(6):2641-2649.
[34] HE C,CARTER A B. The metabolic prospective and Redox regulation of macrophage polarization[J]. J Clin Cell Immunol,2015,6(6):371.
[35] GRIFFITHS H R,GAO D,PARARASA C. Redox regulation in metabolic programming and inflammation[J]. Redox Biol,2017,12(1):50-57.

M1型巨噬细胞糖代谢重编程机制及其在炎症启动中的关键作用

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