title: Combined arginine and glutamine decrease release of de novo synthesized leukotrienes and expression of proinflammatory cytokines in activated human intestinal mast cells.
abstract: OBJECTIVE
  Glutamine and arginine modulate inflammatory responses of epithelial cells and monocytes. Here, we studied the response of human mast cells to pharmacological doses of arginine and glutamine.
  
  
  METHODS
  Mast cells isolated from intestinal tissue were incubated with physiological doses of arginine (0.1 mmol/L) and glutamine (0.6 mmol/L) or with pharmacological doses of arginine (2 mmol/L) and glutamine (10 mmol/L) for 18 h. Following stimulation by IgE receptor crosslinking mast cell mediators were measured by enzymatic assay, ELISA, multiplex bead immunoassay, or real-time RT-PCR, and activation of intracellular signaling molecules was determined using proteome profiler array or immunoblotting.
  
  
  RESULTS
  We found that the combined challenge of mast cells with pharmacological doses of arginine and glutamine caused a decrease in induced release of de novo synthesized leukotriene C(4) but not of pre-stored β-hexosaminidase. Moreover, we found reduced expression of chemokines monocyte chemoattractant protein-1 (CCL2), macrophage inflammatory protein-1β (CCL4), IL-8 (CXCL8), and TNF in response to high doses of both amino acids. The anti-inflammatory effects of arginine and glutamine were associated with decreased activation levels of signaling molecules known to be involved in mast cell cytokine expression such as MAPK family members extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38, and the protein kinase B (Akt).
  
  
  CONCLUSIONS
  Arginine and glutamine attenuate IgE-dependent human mast cell activation by decreasing lipid mediator release and expression of proinflammatory cytokines.
authors.affiliation: Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Lechowski
authors.forename: Katharina
authors.initials: K
authors.lastname: Feilhauer
authors.forename: Ludger
authors.initials: L
authors.lastname: Staib
authors.forename: Moïse
authors.initials: M
authors.lastname: Coëffier
authors.forename: Stephan C
authors.initials: SC
authors.lastname: Bischoff
authors.forename: Axel
authors.initials: A
authors.lastname: Lorentz
mesh_terms: D001120:Arginine / Q000008:administration & dosage*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D054407:Chemokine CCL4 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005260:Female; D005973:Glutamine / Q000008:administration & dosage*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007422:Intestines / Q000166:cytology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D017997:Leukotriene C4 / Q000096:biosynthesis*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D017455:Receptors, IgE / Q000378:metabolism; D015398:Signal Transduction; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D054407:Chemokine CCL4; D016207:Cytokines; D016209:Interleukin-8; D017455:Receptors, IgE; D005973:Glutamine; D017997:Leukotriene C4; D001120:Arginine; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D001619:beta-N-Acetylhexosaminidases