| First Author | Sag D | Year | 2008 |
| Journal | J Immunol | Volume | 181 |
| Issue | 12 | Pages | 8633-41 |
| PubMed ID | 19050283 | Mgi Jnum | J:142055 |
| Mgi Id | MGI:3820343 | Doi | 10.4049/jimmunol.181.12.8633 |
| Citation | Sag D, et al. (2008) Adenosine 5'-monophosphate-activated protein kinase promotes macrophage polarization to an anti-inflammatory functional phenotype. J Immunol 181(12):8633-41 |
| abstractText | 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 TGFbeta) resulted in the rapid phosphorylation/activation of AMPK, whereas stimulation of macrophages with a proinflammatory stimulus (LPS) resulted in AMPK dephosphorylation/inactivation. Inhibition of AMPKalpha expression by RNA interference dramatically increased the mRNA levels of LPS-induced TNF-alpha, IL-6, and cyclooxygenase-2. Likewise, expression of a dominant negative AMPKalpha1 in macrophages enhanced TNF-alpha 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 AMPKalpha1 resulted in decreased LPS-induced TNF-alpha and IL-6 production, and heightened production of IL-10. In addition, we found that AMPK negatively regulated LPS-induced IkappaB-alpha degradation and positively regulated Akt activation, accompanied by inhibition of glycogen synthase kinase beta 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. |
