title: Glutamine Prevents Late-Phase Anaphylaxis via MAPK Phosphatase 1-Dependent Cytosolic Phospholipase A2 Deactivation.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Immunology, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Hae-Kyoung
authors.initials: HK
authors.lastname: Kim
authors.forename: Chang-Ho
authors.initials: CH
authors.lastname: Song
authors.forename: Yun-Soo
authors.initials: YS
authors.lastname: Bae
authors.forename: Suhn-Young
authors.initials: SY
authors.lastname: Im
authors.forename: Hern-Ku
authors.initials: HK
authors.lastname: Lee
mesh_terms: D000707:Anaphylaxis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000517:prevention & control; D000818:Animals; D004195:Disease Models, Animal; D054638:Dual Specificity Phosphatase 1 / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005973:Glutamine / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D054510:Phospholipases A2, Cytosolic / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010972:Platelet Activating Factor / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D010972:Platelet Activating Factor; D034741:RNA, Small Interfering; D005973:Glutamine; D007975:Leukotriene B4; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D054510:Phospholipases A2, Cytosolic; D054638:Dual Specificity Phosphatase 1