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Combined arginine and glutamine decrease release of de novo synthesized leukotrienes and expression of proinflammatory cytokines in activated human intestinal mast cells

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Abstract

Purpose

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 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).

Conclusion

Arginine and glutamine attenuate IgE-dependent human mast cell activation by decreasing lipid mediator release and expression of proinflammatory cytokines.

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Acknowledgments

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.

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Authors and Affiliations

  1. Department of Nutritional Medicine, University of Hohenheim, Fruwirthstraße 12, 70593, Stuttgart, Germany

    Sandra Lechowski, Stephan C. Bischoff & Axel Lorentz

  2. Clinic for Visceral Surgery, Katharinen Hospital, Kriegsbergstraße 60, 70174, Stuttgart, Germany

    Katharina Feilhauer

  3. Clinic for Visceral Surgery, Klinikum Esslingen, Hirschlandstraße 97, 73730, Esslingen, Germany

    Ludger Staib

  4. Appareil Digestif Environnement Nutrition ADEN EA4311, Institute for Biomedical Research, European Institute for Peptide Research (IFRMP 23), Rouen University and Rouen University Hospital, 22, Bld Gambetta, 76183, Rouen Cedex, France

    Moïse Coëffier

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  1. Sandra Lechowski
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  2. Katharina Feilhauer
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  4. Moïse Coëffier
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  5. Stephan C. Bischoff
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Correspondence to Axel Lorentz.

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Lechowski, S., Feilhauer, K., Staib, L. et al. Combined arginine and glutamine decrease release of de novo synthesized leukotrienes and expression of proinflammatory cytokines in activated human intestinal mast cells. Eur J Nutr 52, 505–512 (2013). https://doi.org/10.1007/s00394-012-0353-1

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  • DOI: https://doi.org/10.1007/s00394-012-0353-1

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