AMP-activated protein kinase promotes macrophage polarization to an anti-inflammatory functional phenotype

By Duygu Sag, David Carling, R. Stout, J. Suttles. Journal of Immunology, 2008

725 citations recorded by the source corpus.

Herein, we demonstrate a role of AMP-activated protein kinase (AMPK) as a potent counterregulator of inflammatory signaling pathways in macrophages. Stimulation of macrophages with anti-inflammatory cytokines (i.e., IL-10 and TGFβ) resulted in the rapid phosphorylation/activation of AMPK, whereas stimulation of macrophages with a proinflammatory stimulus (LPS) resulted in AMPK dephosphorylation/inactivation. Inhibition of AMPKα expression by RNA interference dramatically increased the mRNA levels of LPS-induced TNF-α, IL-6, and cyclooxygenase-2. Likewise, expression of a dominant negative AMPKα1 in macrophages enhanced TNF-α and IL-6 protein synthesis in response to LPS stimulation, while diminishing the production of IL-10. In contrast, transfection of macrophages with a constitutively active form of AMPKα1 resulted in decreased LPS-induced TNF-α and IL-6 production, and heightened production of IL-10. In addition, we found that AMPK negatively regulated LPS-induced IκB-α degradation and positively regulated Akt activation, accompanied by inhibition of glycogen synthase kinase β and activation of CREB. Thus, AMPK directs signaling pathways in macrophages in a manner that suppresses proinflammatory responses and promotes macrophage polarization to an anti-inflammatory functional phenotype.

Subfields: Epidemiology, Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/e1ae64bfc57c2415bea09d3bfa1ede9f8863062a

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In Epidemiology

1. H. Fang
2. J. Hyttinen
3. R. L. Judd
4. Antero Salminen
5. K. Kaarniranta

In Immunology

1. H. Fang
2. R. L. Judd
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In Molecular Biology

1. H. Fang
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Citations in the corpus

• AMP-activated protein kinase inhibits NF-κB signaling and inflammation: impact on healthspan and lifespan (2011, background): “[29] observed that IL-10 and transforming growth factor-β (TGF-β), two anti-inflammatory cytokines, stimulated a rapid phosphorylation and activation of AMPK whereas a proinflammatory insult with LPS decreased the AMPK activity in mouse and human macrophages.”
• Adiponectin Regulation and Function (2018, positive): “Full length adiponectin can also directly stimulate M1 → M2 polarization through AdipoR2 → AMPK activation (195), which promotes signaling pathways in macrophages to an anti-inflammatory state (276).”