title: Akt Signaling Pathway in Macrophage Activation and M1/M2 Polarization.
abstract: Macrophages become activated initiating innate immune responses. Depending on the signals, macrophages obtain an array of activation phenotypes, described by the broad terms of M1 or M2 phenotype. The PI3K/Akt/mTOR pathway mediates signals from multiple receptors including insulin receptors, pathogen-associated molecular pattern receptors, cytokine receptors, adipokine receptors, and hormones. As a result, the Akt pathway converges inflammatory and metabolic signals to regulate macrophage responses modulating their activation phenotype. Akt is a family of three serine-threonine kinases, Akt1, Akt2, and Akt3. Generation of mice lacking individual Akt, PI3K, or mTOR isoforms and utilization of RNA interference technology have revealed that Akt signaling pathway components have distinct and isoform-specific roles in macrophage biology and inflammatory disease regulation, by controlling inflammatory cytokines, miRNAs, and functions including phagocytosis, autophagy, and cell metabolism. Herein, we review the current knowledge on the role of the Akt signaling pathway in macrophages, focusing on M1/M2 polarization and highlighting Akt isoform-specific functions.
authors.affiliation: Laboratory of Clinical Chemistry, School of Medicine, University of Crete, Heraklion 71003, Greece; and.|Laboratory of Intensive Care Medicine, School of Medicine, University of Crete, Heraklion 71003, Greece.
authors.forename: Eleni
authors.identifier: 0000-0003-4026-0328
authors.initials: E
authors.lastname: Vergadi
authors.affiliation: Laboratory of Clinical Chemistry, School of Medicine, University of Crete, Heraklion 71003, Greece; and.
authors.forename: Eleftheria
authors.identifier: 0000-0002-8441-298X
authors.initials: E
authors.lastname: Ieronymaki
authors.affiliation: Laboratory of Clinical Chemistry, School of Medicine, University of Crete, Heraklion 71003, Greece; and.
authors.forename: Konstantina
authors.identifier: 0000-0001-7446-0999
authors.initials: K
authors.lastname: Lyroni
authors.affiliation: Laboratory of Intensive Care Medicine, School of Medicine, University of Crete, Heraklion 71003, Greece.
authors.forename: Katerina
authors.initials: K
authors.lastname: Vaporidi
authors.affiliation: Laboratory of Clinical Chemistry, School of Medicine, University of Crete, Heraklion 71003, Greece; and tsatsani@uoc.gr.
authors.forename: Christos
authors.identifier: 0000-0003-1214-4151
authors.initials: C
authors.lastname: Tsatsanis
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology; D001343:Autophagy; D016764:Cell Polarity; D004731:Endotoxins / Q000633:toxicity; D006801:Humans; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000502:physiology; D010587:Phagocytosis; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000502:physiology
chemical_list: D001057:Apolipoproteins E; D004731:Endotoxins; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D058570:TOR Serine-Threonine Kinases