Glutamine Prevents Late-Phase Anaphylaxis via MAPK Phosphatase 1-Dependent Cytosolic Phospholipase A2 Deactivation

• Published in: International archives of allergy and immunology Vol. 171; no. 1; p. 61
• Main Authors: Kim, Hae-Kyoung, Song, Chang-Ho, Bae, Yun-Soo, Im, Suhn-Young, Lee, Hern-Ku
• Format: Journal Article
• Language: English
• Published: Switzerland 2016
• Subjects: Anaphylaxis - genetics; Anaphylaxis - immunology; Anaphylaxis - metabolism; Anaphylaxis - prevention & control; Animals; Disease Models, Animal; Dual Specificity Phosphatase 1 - metabolism; Enzyme Activation - drug effects; Extracellular Signal-Regulated MAP Kinases - metabolism; Female; Glutamine - pharmacology; Leukotriene B4 - blood; Mice; Mice, Knockout; p38 Mitogen-Activated Protein Kinases - metabolism; Phospholipases A2, Cytosolic - genetics; Phospholipases A2, Cytosolic - metabolism; Phosphorylation - drug effects; Platelet Activating Factor - metabolism; RNA, Small Interfering - genetics
• ISSN: 1423-0097
• DOI: 10.1159/000452103

Cytosolic phospholipase A2 (cPLA2) plays a key role in the development of late-phase anaphylaxis. L-Glutamine (Gln), a nonessential amino acid, has anti-inflammatory activity via inhibiting cPLA2. We used a penicillin-induced murine model of anaphylaxis, and late-phase anaphylaxis was quantified by measuring the increase in the hematocrit (Ht) value. Various inhibitors, small interfering RNA, and knockout mice were used in inhibition experiments. Phosphorylation and protein expression of cPLA2, ERK, and MAPK phosphatase 1 (MKP-1) were detected by Western blotting. Leukotriene (LT) B4 was found to be another potent inducer of late-phase anaphylaxis besides the known mediator platelet-activating-factor (PAF). Gln efficiently prevented late-phase anaphylaxis when it was administered up to 3 h after challenge injection via inhibiting cPLA2. Inhibition studies indicated that p38 MAPK was the major upstream regulator of cPLA2. Gln dephosphorylated p38 and cPLA2 via up-regulating the negative regulator of p38 MAPK, i.e., MKP-1 protein. MKP-1 blockade abrogated all the effects of Gln. Of the cPLA2 metabolites, PAF and LTB4 play a key role in the development of late-phase anaphylaxis, and Gln prevents the reaction via MKP-1-dependent deactivation of cPLA2.