Effects of Metabolism on Macrophage Polarization Under Different Disease Backgrounds

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2022 Aug 1

PMID 35911719

Authors

Jia-Xue Sun

Xiang-Hong Xu

Liping Jin

Affiliations

Soon will be listed here.

Abstract

Macrophages are versatile immune cells associated with various diseases, and their phenotypes and functions change on the basis of the surrounding environments. Reprogramming of metabolism is required for the proper polarization of macrophages. This review will focus on basic metabolic pathways, the effects of key enzymes and specific products, relationships between cellular metabolism and macrophage polarization in different diseases and the potential prospect of therapy targeted key metabolic enzymes. In particular, the types and characteristics of macrophages at the maternal-fetal interface and their effects on a successful conception will be discussed.

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References

Menegaut L, Jalil A, Thomas C, Masson D . Macrophage fatty acid metabolism and atherosclerosis: The rise of PUFAs. Atherosclerosis. 2019; 291:52-61. DOI: 10.1016/j.atherosclerosis.2019.10.002. View

Gao F, Tang Y, Liu W, Zou M, Huang C, Liu C . Intra/Extracellular Lactic Acid Exhaustion for Synergistic Metabolic Therapy and Immunotherapy of Tumors. Adv Mater. 2019; 31(51):e1904639. DOI: 10.1002/adma.201904639. View

Das Gupta K, Shakespear M, Curson J, Murthy A, Iyer A, Hodson M . Class IIa Histone Deacetylases Drive Toll-like Receptor-Inducible Glycolysis and Macrophage Inflammatory Responses via Pyruvate Kinase M2. Cell Rep. 2020; 30(8):2712-2728.e8. DOI: 10.1016/j.celrep.2020.02.007. View

Wu K, Lin K, Li X, Yuan X, Xu P, Ni P . Redefining Tumor-Associated Macrophage Subpopulations and Functions in the Tumor Microenvironment. Front Immunol. 2020; 11:1731. PMC: 7417513. DOI: 10.3389/fimmu.2020.01731. View

Calle R, Amin N, Carvajal-Gonzalez S, Ross T, Bergman A, Aggarwal S . ACC inhibitor alone or co-administered with a DGAT2 inhibitor in patients with non-alcoholic fatty liver disease: two parallel, placebo-controlled, randomized phase 2a trials. Nat Med. 2021; 27(10):1836-1848. DOI: 10.1038/s41591-021-01489-1. View

Yu X, Li Z, Zhang Y, Xu M, Che Y, Tian X . β-elemene inhibits radiation and hypoxia-induced macrophages infiltration via Prx-1/NF-κB/HIF-1α signaling pathway. Onco Targets Ther. 2019; 12:4203-4211. PMC: 6549424. DOI: 10.2147/OTT.S196910. View

Bailey J, Diotallevi M, Nicol T, McNeill E, Shaw A, Chuaiphichai S . Nitric Oxide Modulates Metabolic Remodeling in Inflammatory Macrophages through TCA Cycle Regulation and Itaconate Accumulation. Cell Rep. 2019; 28(1):218-230.e7. PMC: 6616861. DOI: 10.1016/j.celrep.2019.06.018. View

Esteban-Martinez L, Sierra-Filardi E, McGreal R, Salazar-Roa M, Marino G, Seco E . Programmed mitophagy is essential for the glycolytic switch during cell differentiation. EMBO J. 2017; 36(12):1688-1706. PMC: 5470043. DOI: 10.15252/embj.201695916. View

Essandoh K, Li Y, Huo J, Fan G . MiRNA-Mediated Macrophage Polarization and its Potential Role in the Regulation of Inflammatory Response. Shock. 2016; 46(2):122-31. PMC: 4949115. DOI: 10.1097/SHK.0000000000000604. View

10.

Hao J, Hu Y, Li Y, Zhou Q, Lv X . Involvement of JNK signaling in IL4-induced M2 macrophage polarization. Exp Cell Res. 2017; 357(2):155-162. DOI: 10.1016/j.yexcr.2017.05.010. View

11.

Zhang Q, Wang H, Mao C, Sun M, Dominah G, Chen L . Fatty acid oxidation contributes to IL-1β secretion in M2 macrophages and promotes macrophage-mediated tumor cell migration. Mol Immunol. 2017; 94:27-35. PMC: 5801116. DOI: 10.1016/j.molimm.2017.12.011. View

12.

Yu Y, Cai W, Zhou J, Lu H, Wang Y, Song Y . Anti-arthritis effect of berberine associated with regulating energy metabolism of macrophages through AMPK/ HIF-1α pathway. Int Immunopharmacol. 2020; 87:106830. DOI: 10.1016/j.intimp.2020.106830. View

13.

Ahmed M, de Winther M, Van den Bossche J . Epigenetic mechanisms of macrophage activation in type 2 diabetes. Immunobiology. 2016; 222(10):937-943. DOI: 10.1016/j.imbio.2016.08.011. View

14.

Wu J, Huang T, Hsieh Y, Wang Y, Yen C, Lee G . Cancer-Derived Succinate Promotes Macrophage Polarization and Cancer Metastasis via Succinate Receptor. Mol Cell. 2019; 77(2):213-227.e5. DOI: 10.1016/j.molcel.2019.10.023. View

15.

Spiller K, Wrona E, Romero-Torres S, Pallotta I, Graney P, Witherel C . Differential gene expression in human, murine, and cell line-derived macrophages upon polarization. Exp Cell Res. 2015; 347(1):1-13. DOI: 10.1016/j.yexcr.2015.10.017. View

16.

Abu Rmaileh A, Solaimuthu B, Tanna M, Khatib A, Ben Yosef M, Hayashi A . Large-Scale Differential Gene Expression Transcriptomic Analysis Identifies a Metabolic Signature Shared by All Cancer Cells. Biomolecules. 2020; 10(5). PMC: 7277211. DOI: 10.3390/biom10050701. View

17.

Marin-Hernandez A, Gallardo-Perez J, Ralph S, Rodriguez-Enriquez S, Moreno-Sanchez R . HIF-1alpha modulates energy metabolism in cancer cells by inducing over-expression of specific glycolytic isoforms. Mini Rev Med Chem. 2009; 9(9):1084-101. DOI: 10.2174/138955709788922610. View

18.

Nakayama Y, Fujiu K, Yuki R, Oishi Y, Morioka M, Isagawa T . A long noncoding RNA regulates inflammation resolution by mouse macrophages through fatty acid oxidation activation. Proc Natl Acad Sci U S A. 2020; 117(25):14365-14375. PMC: 7322040. DOI: 10.1073/pnas.2005924117. View

19.

Zhang S, Jiao Y, Li C, Liang X, Jia H, Nie Z . Dimethyl Itaconate Alleviates the Inflammatory Responses of Macrophages in Sepsis. Inflammation. 2020; 44(2):549-557. DOI: 10.1007/s10753-020-01352-4. View

20.

Chen F, Chen J, Yang L, Liu J, Zhang X, Zhang Y . Extracellular vesicle-packaged HIF-1α-stabilizing lncRNA from tumour-associated macrophages regulates aerobic glycolysis of breast cancer cells. Nat Cell Biol. 2019; 21(4):498-510. DOI: 10.1038/s41556-019-0299-0. View