The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Akt1 and Akt2 protein kinases differentially contribute to macrophage polarization
Open accessAbstract
Activated macrophages are described as classically activated or M1 type and alternatively activated or M2 type, depending on their response to proinflammatory stimuli and the expression of genetic markers including iNOS, arginase1, Ym1, and Fizz1. Here we report that Akt kinases differentially contribute to macrophage polarization, with Akt1 ablation giving rise to an M1 and Akt2 ablation resulting in an M2 phenotype. Accordingly, Akt2 −/− mice were more resistant to LPS-induced endotoxin shock and to dextran sulfate sodium (DSS)-induced colitis than wild-type mice, whereas Akt1 −/− mice were more sensitive. Cell depletion and reconstitution experiments in a DSS-induced colitis model confirmed that the effect was macrophage-dependent. Gene-silencing studies showed that the M2 phenotype of Akt2 −/− macrophages was cell autonomous. The microRNA miR-155, whose expression was repressed in naive and in LPS-stimulated Akt2 −/− macrophages, and its target C/EBPβ appear to play a key role in this process. C/EBPβ, a hallmark of M2 macrophages that regulates Arg1, was up-regulated upon Akt2 ablation or silencing. Overexpression or silencing of miR-155 confirmed its central role in Akt isoform-dependent M1/M2 polarization of macrophages.
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Citations
Cites
Protective and pathogenic functions of macrophage subsets
Murray, P. J., & Wynn, T. A. (2011) · Nature Reviews Immunology · doi:10.1038/nri3073 · Cited by 5,269
Alternative activation of macrophages: mechanism and functions
Gordon, S., & Martinez, F. O. (2010) · Immunity · doi:10.1016/j.immuni.2010.05.007 · Cited by 4,197
Transcriptional regulation of macrophage polarization: enabling diversity with identity
Lawrence, T., & Natoli, G. (2011) · Nature Reviews Immunology · doi:10.1038/nri3088 · Cited by 2,284
Adiponectin Promotes Macrophage Polarization toward an Anti-inflammatory Phenotype
Ohashi, K., Parker, J. L., Ouchi, N., Higuchi, A., Vita, J. A., Gokce, N., Pedersen, A. A., Kalthoff, C., Tullin, S., Sams, A., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.088708 · Cited by 646 · cited 1×
“Leptin and adiponectin also regulate arginase expression and macrophage polarization to the M2 phenotype (16).”
BackgroundRuffell, D., Mourkioti, F., Gambardella, A., Kirstetter, P., Lopez, R. G., Rosenthal, N., & Nerlov, C. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908641106 · Cited by 626
The Kinase Akt1 Controls Macrophage Response to Lipopolysaccharide by Regulating MicroRNAs
Androulidaki, A., Iliopoulos, D., Arranz, A., Doxaki, C., Schworer, S., Zacharioudaki, V., Margioris, A. N., Tsichlis, P. N., & Tsatsanis, C. (2009) · Immunity · doi:10.1016/j.immuni.2009.06.024 · Cited by 581
Self-citationProtein Kinase Bα/Akt1 Regulates Placental Development and Fetal Growth
Yang, Z.-Z., Tschopp, O., Hemmings-Mieszczak, M., Feng, J., Brodbeck, D., Perentes, E., & Hemmings, B. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302847200 · Cited by 384
Cited by
Macrophage activation and polarization: nomenclature and experimental guidelines
Murray, P. J., Allen, J. E., Biswas, S. K., Fisher, E. A., Gilroy, D. W., Goerdt, S., Gordon, S., Hamilton, J. A., Ivashkiv, L. B., Lawrence, T., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.06.008 · Cited by 6,337
AKT/PKB Signaling: Navigating the Network
Manning, B. D., & Toker, A. (2017) · Cell · doi:10.1016/j.cell.2017.04.001 · Cited by 3,772
Murray, P. J. (2017) · Annual Review of Physiology · doi:10.1146/annurev-physiol-022516-034339 · Cited by 2,981
The metabolic signature of macrophage responses
Viola, A., Munari, F., Sánchez-Rodríguez, R., Scolaro, T., & Castegna, A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01462 · Cited by 2,021
Macrophage Polarization States in the Tumor Microenvironment
Boutilier, A. J., & Elsawa, S. F. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22136995 · Cited by 1,631
Metadata
- Authors
- Arranz, A., Doxaki, C., Vergadi, E., Martinez de la Torre, Y., Vaporidi, K., Lagoudaki, E. D., Ieronymaki, E., Androulidaki, A., Venihaki, M., Margioris, A. N., Stathopoulos, E. N., Tsichlis, P. N., & Tsatsanis, C.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2012-05-30
- Volume
- 109
- Issue
- 24
- Pages
- 9517-9522
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1981056356
- Cited by
- 608
- References
- 7
- FWCI
- 12.82
- Type
- journal article
- Language
- en
- Open access
- bronze
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