1. Glutamine up-regulates MAPK phosphatase-1 induction via activation of Ca
- Author
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Otgonzaya, Ayush, Zhe Wu, Jin, Hae-Kyoung, Kim, Yu-Rim, Shin, Suhn-Young, Im, and Hern-Ku, Lee
- Subjects
Asp, aspartate ,CD, contact dermatitis ,DNFB, 1-fluoro-2,4-dinitrobenzene ,MKP-1, MAPK phosphatase-1 ,Ras/c-Raf/MEK/ERK, extracellular-signal-regulated kinase ,DMSO, dimethyl sulfoxide ,Ala, alanine ,CaR, Ca2+-sensing receptor ,[Ca2+]i, intracellular calcium concentration ,ERK, extracellular signal-regulated kinase ,L-Glutamine ,ESR, ear swelling response ,cPLA2, cytoplasmic phospholipase A2 ,PEI, polyethyleneimine ,CaM, calmodulin ,Glu, glutamate ,Gly, glycine ,BAPTA, 1,2-bis(o-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid tetraacetoxymethylester ,Mitogen-activated protein kinase ,AP-1, activating protein 1 ,siRNA, small interfering RNA ,JNK, c-Jun N-terminal kinase ,MAPK Phosphatase-1 ,Gln, L-glutamine ,H&E, hematoxylin and eosin ,LPS, lipopolysaccharides ,Research Article ,MAPK, mitogen activated protein kinase - Abstract
The non-essential amino acid L-glutamine (Gln) displays potent anti-inflammatory activity by deactivating p38 mitogen activating protein kinase and cytosolic phospholipase A2 via induction of MAPK phosphatase-1 (MKP-1) in an extracellular signal-regulated kinase (ERK)-dependent way. In this study, the mechanism of Gln-mediated ERK-dependency in MKP-1 induction was investigated. Gln increased ERK phosphorylation and activity, and phosphorylations of Ras, c-Raf, and MEK, located in the upstream pathway of ERK, in response to lipopolysaccharidein vitro and in vivo. Gln-induced dose-dependent transient increases in intracellular calcium ([Ca2+]i) in MHS macrophage cells. Ionomycin increased [Ca2+]i and activation of Ras → ERK pathway, and MKP-1 induction, in the presence, but not in the absence, of LPS. The Gln-induced pathways involving Ca2+→ MKP-1 induction were abrogated by a calcium blocker. Besides Gln, other amino acids including L-phenylalanine and l-cysteine (Cys) also induced Ca2+ response, activation of Ras → ERK, and MKP-1 induction, albeit to a lesser degree. Gln and Cys were comparable in suppression against 2, 4-dinitrofluorobenzene-induced contact dermatitis. Gln-mediated, but not Cys-mediated, suppression was abolished by MKP-1 small interfering RNA. These data indicate that Gln induces MKP-1 by activating Ca2+→ ERK pathway, which plays a key role in suppression of inflammatory reactions.
- Published
- 2016