Gene interactions and pathways from curated databases and text-mining
J Immunol 2008, PMID: 19050283

Adenosine 5'-monophosphate-activated protein kinase promotes macrophage polarization to an anti-inflammatory functional phenotype.

Sag, Duygu; Carling, David; Stout, Robert D; Suttles, Jill

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.

Diseases/Pathways annotated by Medline MESH: Inflammation
Document information provided by NCBI PubMed

Text Mining Data

TNF-alpha → LPS: " Inhibition of AMPKalpha expression by RNA interference dramatically increased the mRNA levels of LPS induced TNF-alpha , IL-6, and cyclooxygenase-2 "

IL-6 → LPS: " Inhibition of AMPKalpha expression by RNA interference dramatically increased the mRNA levels of LPS induced TNF-alpha, IL-6 , and cyclooxygenase-2 "

cyclooxygenase-2 → LPS: " Inhibition of AMPKalpha expression by RNA interference dramatically increased the mRNA levels of LPS induced TNF-alpha, IL-6, and cyclooxygenase-2 "

TNF-alpha ⊣ IL-10: " 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 "

IL-6 ⊣ IL-10: " 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 "

TNF-alpha → LPS: " 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 "

IL-6 → LPS: " 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 "

TNF-alpha → LPS: " 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 "

IL-10 → LPS: " 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 "

IL-6 → LPS: " 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 "

IkappaB-alpha → LPS: " 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 "

IkappaB-alpha → AMPK: " 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 "

Akt — IkappaB-alpha: " 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 "

Akt — AMPK: " 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 "

Manually curated Databases

No curated data.