Combined arginine and glutamine decrease release of de novo synthesized leukotrienes and expression of proinflammatory cytokines in activated human intestinal mast cells
- 985 Downloads
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.
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.
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 C4 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).
Arginine and glutamine attenuate IgE-dependent human mast cell activation by decreasing lipid mediator release and expression of proinflammatory cytokines.
KeywordsArginine Glutamine Intestinal mucosa Mast cell Cytokine expression
The present work was supported by the Centre for Nutritional Medicine (ZEM 16AIII).
Conflict of interest
The authors declare that they have no conflict of interests.
- 3.Lecleire S, Hassan A, Marion-Letellier R, Antonietti M, Savoye G, Bole-Feysot C, Lerebours E, Ducrotte P, Dechelotte P, Coeffier M (2008) Combined glutamine and arginine decrease proinflammatory cytokine production by biopsies from Crohn’s patients in association with changes in nuclear factor-kappaB and p38 mitogen-activated protein kinase pathways. J Nutr 138:2481–2486CrossRefGoogle Scholar
- 5.Suchner U, Heyland DK, Peter K (2002) Immune-modulatory actions of arginine in the critically ill. Br J Nutr 87(Suppl 1):121–132Google Scholar
- 11.Boelens PG, Houdijk AP, Fonk JC, Nijveldt RJ, Ferwerda CC, Von Blomberg-Van Der Flier BM, Thijs LG, Haarman HJ, Puyana JC, Van Leeuwen PA (2002) Glutamine-enriched enteral nutrition increases HLA-DR expression on monocytes of trauma patients. J Nutr 132:2580–2586Google Scholar
- 13.Kretzmann NA, Fillmann H, Mauriz JL, Marroni CA, Marroni N, Gonzalez-Gallego J, Tunon MJ (2008) Effects of glutamine on proinflammatory gene expression and activation of nuclear factor kappa B and signal transducers and activators of transcription in TNBS-induced colitis. Inflamm Bowel Dis 14:1504–1513CrossRefGoogle Scholar
- 19.He SH (2004) Key role of mast cells and their major secretory products in inflammatory bowel disease. World J Gastroenterol 10:309–318Google Scholar
- 21.Sellge G, Bischoff SC (2006) Isolation, culture, and characterization of intestinal mast cells. Methods Mol Biol 315:123–138Google Scholar
- 23.Lorentz A, Schwengberg S, Sellge G, Manns MP, Bischoff SC (2000) Human intestinal mast cells are capable of producing different cytokine profiles, role of IgE receptor cross-linking and IL-4. J Immunol 164:43–48Google Scholar
- 28.Schwartz LB, Austen KF, Wasserman SI (1979) Immunologic release of beta-hexosaminidase and beta-glucuronidase from purified rat serosal mast cells. J Immunol 123:1445–1450Google Scholar
- 30.Lorentz A, Wilke M, Sellge G, Worthmann H, Klempnauer J, Manns MP, Bischoff SC (2005) IL-4-induced priming of human intestinal mast cells for enhanced survival and Th2 cytokine generation is reversible and associated with increased activity of ERK1/2 and c-Fos. J Immunol 174:6751–6756Google Scholar
- 31.Hubert-Buron A, Leblond J, Jacquot A, Ducrotte P, Dechelotte P, Coeffier M (2006) Glutamine pretreatment reduces IL-8 production in human intestinal epithelial cells by limiting IkappaBalpha ubiquitination. J Nutr 136:1461–1465Google Scholar
- 33.Waetzig GH, Seegert D, Rosenstiel P, Nikolaus S, Schreiber S (2002) p38 mitogen-activated protein kinase is activated and linked to TNF-alpha signaling in inflammatory bowel disease. J Immunol 168:5342–5351Google Scholar
- 34.Lockyer HM, Tran E, Nelson BH (2007) STAT5 is essential for Akt/p70S6 kinase activity during IL-2-induced lymphocyte proliferation. J Immunol 179:5301–5308Google Scholar
- 35.Ruiz PA, Haller D (2006) Functional diversity of flavonoids in the inhibition of the proinflammatory NF-kappaB, IRF, and Akt signaling pathways in murine intestinal epithelial cells. J Nutr 136:664–671Google Scholar
- 42.Koon HW, Zhao D, Zhan Y, Rhee SH, Moyer MP, Pothoulakis C (2006) Substance P stimulates cyclooxygenase-2 and prostaglandin E2 expression through JAK-STAT activation in human colonic epithelial cells. J Immunol 176:5050–5059Google Scholar