| First Author | Mieulet V | Year | 2010 |
| Journal | Sci Signal | Volume | 3 |
| Issue | 135 | Pages | ra61 |
| PubMed ID | 20716763 | Mgi Jnum | J:259459 |
| Mgi Id | MGI:6141031 | Doi | 10.1126/scisignal.2000934 |
| Citation | Mieulet V, et al. (2010) TPL-2-mediated activation of MAPK downstream of TLR4 signaling is coupled to arginine availability. Sci Signal 3(135):ra61 |
| abstractText | The innate immune response is influenced by the nutrient status of the host. Mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinase 1 (ERK1) and ERK2, are activated after the stimulation of macrophages with bacterial lipopolysaccharide (LPS) and are necessary for the optimal production of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha). We uncovered a role for the extracellular nutrient arginine in the activation of ERK1/2 in LPS-stimulated macrophages. Arginine facilitated the activation of MAPKs by preventing the dephosphorylation and inactivation of the MAPK kinase kinase tumor-promoting locus 2 (TPL-2). Starvation of mice decreased the concentration of arginine in the plasma and impaired the activation of ERK1/2 by LPS. Supplementation of starved mice with arginine promoted the subsequent activation of ERK1/2 and the production of TNF-alpha in response to LPS. Thus, arginine is critical for two aspects of the innate immune response in macrophages: It is the precursor used in the generation of the antimicrobial mediator nitric oxide, and it facilitates MAPK activation and consequently cytokine production. |
