TPL-2-Mediated Activation of MAPK Downstream of TLR4 Signaling Is Coupled to Arginine Availability
Date
2010-08-17ICR Author
Author
Mieulet, V
Yan, L
Choisy, C
Sully, K
Procter, J
Kouroumalis, A
Krywawych, S
Pende, M
Ley, SC
Moinard, C
Lamb, RF
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Research team
Target Validation and DNA Damage Response
Language
eng
License start date
2010-08-17
Citation
SCIENCE SIGNALING, 2010, 3
Publisher
AMER ASSOC ADVANCEMENT SCIENCE