AKT Isoforms in Macrophage Activation, Polarization, and Survival

Overview

Journal Curr Top Microbiol Immunol

Specialties Allergy & Immunology
Microbiology

Date 2022 Oct 15

PMID 36243844

Authors

Ioanna Lapi

Maria G Daskalaki

Konstantinos Axarlis

Eleni Paflioti

Philip N Tsichlis

Eleni Vergadi

Christos Tsatsanis

Affiliations

Soon will be listed here.

Abstract

Macrophages display an array of activation phenotypes depending on the activation signal and the cellular microenvironment. The type and magnitude of the response depend on signaling molecules as well as on the epigenetic and metabolic status of the cells at the time of activation. The AKT family of kinases consists of three isoforms encoded by independent genes possessing similar functions and structures. Generation of research tools such as isoform-specific gene deletion mutant mice and cells and isoform-specific antibodies has allowed us to understand the role of each kinase isoform in macrophage activation and homeostasis. This chapter discusses the current evidence on the role of AKT kinases in macrophage activation, polarization, and homeostasis, highlighting the gaps in knowledge and future challenges in the field.

Citing Articles

Advances in the study of macrophage polarization in inflammatory immune skin diseases.

Xia T, Fu S, Yang R, Yang K, Lei W, Yang Y J Inflamm (Lond). 2023; 20(1):33.

PMID: 37828492 PMC: 10568804. DOI: 10.1186/s12950-023-00360-z.

[Akt2 inhibitor promotes M2 macrophage polarization in rats with periapical inflammation by reducing miR-155-5p expression].

Li J, Yang S, Han Z, Jiang T, Zhu Y, Zhou Z Nan Fang Yi Ke Da Xue Xue Bao. 2023; 43(4):568-576.

PMID: 37202192 PMC: 10202785. DOI: 10.12122/j.issn.1673-4254.2023.04.09.

References

Abdelaziz M, Abdelwahab S, Wan J, Cai W, Huixuan W, Jianjun C . Alternatively activated macrophages; a double-edged sword in allergic asthma. J Transl Med. 2020; 18(1):58. PMC: 7003359. DOI: 10.1186/s12967-020-02251-w. View

Akira S, Takeda K . Toll-like receptor signalling. Nat Rev Immunol. 2004; 4(7):499-511. DOI: 10.1038/nri1391. View

Androulidaki A, Iliopoulos D, Arranz A, Doxaki C, Schworer S, Zacharioudaki V . The kinase Akt1 controls macrophage response to lipopolysaccharide by regulating microRNAs. Immunity. 2009; 31(2):220-31. PMC: 2865583. DOI: 10.1016/j.immuni.2009.06.024. View

Arbibe L, Mira J, Teusch N, Kline L, Guha M, Mackman N . Toll-like receptor 2-mediated NF-kappa B activation requires a Rac1-dependent pathway. Nat Immunol. 2001; 1(6):533-40. DOI: 10.1038/82797. View

Arranz A, Androulidaki A, Zacharioudaki V, Martinez C, Margioris A, Gomariz R . Vasoactive intestinal peptide suppresses toll-like receptor 4 expression in macrophages via Akt1 reducing their responsiveness to lipopolysaccharide. Mol Immunol. 2008; 45(10):2970-80. DOI: 10.1016/j.molimm.2008.01.023. View

Arts R, Novakovic B, Ter Horst R, Carvalho A, Bekkering S, Lachmandas E . Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity. Cell Metab. 2016; 24(6):807-819. PMC: 5742541. DOI: 10.1016/j.cmet.2016.10.008. View

Artyomov M, Sergushichev A, Schilling J . Integrating immunometabolism and macrophage diversity. Semin Immunol. 2016; 28(5):417-424. PMC: 5333784. DOI: 10.1016/j.smim.2016.10.004. View

Baardman J, Licht I, de Winther M, Van den Bossche J . Metabolic-epigenetic crosstalk in macrophage activation. Epigenomics. 2015; 7(7):1155-64. DOI: 10.2217/epi.15.71. View

Baba A, Ohtake F, Okuno Y, Yokota K, Okada M, Imai Y . PKA-dependent regulation of the histone lysine demethylase complex PHF2-ARID5B. Nat Cell Biol. 2011; 13(6):668-75. DOI: 10.1038/ncb2228. View

10.

Babaev V, Chew J, Ding L, Davis S, Breyer M, Breyer R . Macrophage EP4 deficiency increases apoptosis and suppresses early atherosclerosis. Cell Metab. 2008; 8(6):492-501. PMC: 2614698. DOI: 10.1016/j.cmet.2008.09.005. View

11.

Babaev V, Hebron K, Wiese C, Toth C, Ding L, Zhang Y . Macrophage deficiency of Akt2 reduces atherosclerosis in Ldlr null mice. J Lipid Res. 2014; 55(11):2296-308. PMC: 4617132. DOI: 10.1194/jlr.M050633. View

13.

Babaev V, Yeung M, Erbay E, Ding L, Zhang Y, May J . Jnk1 Deficiency in Hematopoietic Cells Suppresses Macrophage Apoptosis and Increases Atherosclerosis in Low-Density Lipoprotein Receptor Null Mice. Arterioscler Thromb Vasc Biol. 2016; 36(6):1122-31. PMC: 4882236. DOI: 10.1161/ATVBAHA.116.307580. View

14.

Babaev V, Huang J, Ding L, Zhang Y, May J, Linton M . Loss of in Monocyte/Macrophages Suppresses Their Proliferation and Viability Reducing Atherosclerosis in LDLR Null Mice. Front Immunol. 2018; 9:215. PMC: 5816794. DOI: 10.3389/fimmu.2018.00215. View

15.

Babaev V, Ding L, Zhang Y, May J, Ramsey S, Vickers K . Loss of 2 Akt (Protein Kinase B) Isoforms in Hematopoietic Cells Diminished Monocyte and Macrophage Survival and Reduces Atherosclerosis in Ldl Receptor-Null Mice. Arterioscler Thromb Vasc Biol. 2018; 39(2):156-169. PMC: 6344270. DOI: 10.1161/ATVBAHA.118.312206. View

16.

Bade P, Simonetti F, Sans S, Laboudie P, Kissane K, Chappat N . Integrative Analysis of Human Macrophage Inflammatory Response Related to Virulence. Front Immunol. 2021; 12:668060. PMC: 8284339. DOI: 10.3389/fimmu.2021.668060. View

17.

Bala S, Marcos M, Kodys K, Csak T, Catalano D, Mandrekar P . Up-regulation of microRNA-155 in macrophages contributes to increased tumor necrosis factor {alpha} (TNF{alpha}) production via increased mRNA half-life in alcoholic liver disease. J Biol Chem. 2010; 286(2):1436-44. PMC: 3020752. DOI: 10.1074/jbc.M110.145870. View

18.

Bao L, Li X . MicroRNA-32 targeting PTEN enhances M2 macrophage polarization in the glioma microenvironment and further promotes the progression of glioma. Mol Cell Biochem. 2019; 460(1-2):67-79. DOI: 10.1007/s11010-019-03571-2. View

19.

Bekkering S, Arts R, Novakovic B, Kourtzelis I, van der Heijden C, Li Y . Metabolic Induction of Trained Immunity through the Mevalonate Pathway. Cell. 2018; 172(1-2):135-146.e9. DOI: 10.1016/j.cell.2017.11.025. View

20.

Brodbeck D, Cron P, Hemmings B . A human protein kinase Bgamma with regulatory phosphorylation sites in the activation loop and in the C-terminal hydrophobic domain. J Biol Chem. 1999; 274(14):9133-6. DOI: 10.1074/jbc.274.14.9133. View

21.

Byles V, Covarrubias A, Ben-Sahra I, Lamming D, Sabatini D, Manning B . The TSC-mTOR pathway regulates macrophage polarization. Nat Commun. 2013; 4:2834. PMC: 3876736. DOI: 10.1038/ncomms3834. View