| First Author | Carroll KC | Year | 2013 |
| Journal | J Leukoc Biol | Volume | 94 |
| Issue | 6 | Pages | 1113-21 |
| PubMed ID | 23883517 | Mgi Jnum | J:201908 |
| Mgi Id | MGI:5516152 | Doi | 10.1189/jlb.0313157 |
| Citation | Carroll KC, et al. (2013) AMPKalpha1 deficiency amplifies proinflammatory myeloid APC activity and CD40 signaling. J Leukoc Biol 94(6):1113-21 |
| abstractText | AMPK is a serine/threonine kinase that regulates energy homeostasis and metabolic stress in eukaryotes. Previous work from our laboratory, as well as by others, has provided evidence that AMPKalpha1 acts as a negative regulator of TLR-induced inflammatory function. Herein, we demonstrate that AMPKalpha1-deficient macrophages and DCs exhibit heightened inflammatory function and an enhanced capacity for antigen presentation favoring the promotion of Th1 and Th17 responses. Macrophages and DCs generated from AMPKalpha1-deficient mice produced higher levels of proinflammatory cytokines and decreased production of the anti-inflammatory cytokine IL-10 in response to TLR and CD40 stimulation as compared with WT cells. In assays of antigen presentation, AMPKalpha1 deficiency in the myeloid APC and T cell populations contributed to enhanced IL-17 and IFN-gamma production. Focusing on the CD154-CD40 interaction, we found that CD40 stimulation resulted in increased phosphorylation of ERK1/2, p38, and NF-kappaB p65 and decreased activation of the anti-inflammatory Akt -GSK3beta-CREB pathway in DCs deficient for AMPKalpha1. Our data demonstrate that AMPKalpha1 serves to attenuate LPS and CD40-mediated proinflammatory activity of myeloid APCs and that AMPKalpha1 activity in both APC and T cells contributes to T cell functional polarization during antigen presentation. |
