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Investigation of Macrophage Polarization Using Bone Marrow Derived Macrophages
Published on: June 23, 2013
Akt Signaling Pathway in Macrophage Activation and M1/M2 Polarization
Eleni Vergadi1,2, Eleftheria Ieronymaki1, Konstantina Lyroni1
1Laboratory of Clinical Chemistry, School of Medicine, University of Crete, Heraklion 71003, Greece; and.
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.
Insights
The Akt signaling pathway regulates macrophage activation and inflammatory responses. Specific Akt isoforms control distinct functions, influencing M1/M2 polarization and disease.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Macrophages are key immune cells with diverse activation states, M1 and M2.
- The PI3K/Akt/mTOR pathway integrates signals regulating macrophage inflammatory and metabolic functions.
- Akt signaling influences macrophage phenotype and inflammatory disease progression.
Purpose of the Study:
- To review the role of the Akt signaling pathway in macrophage biology.
- To focus on Akt's involvement in M1/M2 polarization.
- To highlight isoform-specific functions of Akt in macrophages.
Main Methods:
- Review of existing literature on Akt signaling in macrophages.
- Analysis of studies utilizing genetic knockout models (Akt, PI3K, mTOR isoforms).
- Examination of RNA interference studies in macrophage research.
Main Results:
- Akt signaling pathway components exhibit distinct, isoform-specific roles.
- Akt isoforms regulate macrophage inflammatory cytokine production and miRNA expression.
- Akt controls critical macrophage functions like phagocytosis, autophagy, and metabolism.
Conclusions:
- The Akt pathway is crucial for modulating macrophage activation states, particularly M1/M2 polarization.
- Understanding Akt isoform-specific functions is vital for regulating inflammatory diseases.
- Targeting specific Akt isoforms may offer therapeutic strategies for immune modulation.
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