European Journal of Nutrition

, Volume 52, Issue 4, pp 1343–1351 | Cite as

Modulation of the nuclear factor-kappa B (NF-κB) signalling pathway by glutamine in peritoneal macrophages of a murine model of protein malnutrition

  • Fabiana da Silva Lima
  • Marcelo Macedo Rogero
  • Mayara Caldas Ramos
  • Primavera Borelli
  • Ricardo Ambrósio Fock
Original Contribution

Abstract

Background and aims

Protein malnutrition affects resistance to infection by impairing the inflammatory response, modifying the function of effector cells, such as macrophages. Recent studies have revealed that glutamine—a non-essential amino acid, which could become conditionally essential in some situations like trauma, infection, post-surgery and sepsis—is able to modulate the synthesis of cytokines. The aim of this study was to evaluate the effect of glutamine on the expression of proteins involved in the nuclear factor-kappa B (NF-κB) signalling pathway of peritoneal macrophages from malnourished mice.

Methods

Two-month-old male Balb/c mice were submitted to protein-energy malnutrition (n = 10) with a low-protein diet containing 2 % protein, whereas control mice (n = 10) were fed a 12 % protein-containing diet. The haemogram and analysis of plasma glutamine and corticosterone were evaluated. Peritoneal macrophages were pre-treated in vitro with glutamine (0, 0.6, 2 and 10 mmol/L) for 24 h and then stimulated with 1.25 μg LPS for 30 min, and the synthesis of TNF-α and IL-1α and the expression of proteins related to the NF-κB pathway were evaluated.

Results

Malnourished animals had anaemia, leucopoenia, lower plasma glutamine and increased corticosterone levels. TNF-α production of macrophages stimulated with LPS was significantly lower in cells from malnourished animals when cultivated in supraphysiological (2 and 10 mmol/L) concentrations of glutamine. Further, glutamine has a dose-dependent effect on the activation of macrophages, in both groups, when stimulated with LPS, inducing a decrease in TNF-α and IL-1α production and negatively modulating the NF-κB signalling pathway.

Conclusions

These data lead us to infer that the protein malnutrition state interferes with the activation of macrophages and that higher glutamine concentrations, in vitro, have the capacity to act negatively in the NF-κB signalling pathway.

Keywords

Protein malnutrition Macrophages Glutamine NF-κB TNF-α IL-1α 

Notes

Acknowledgments

This investigation was supported by grants from the Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP).

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Fabiana da Silva Lima
    • 1
  • Marcelo Macedo Rogero
    • 2
  • Mayara Caldas Ramos
    • 1
  • Primavera Borelli
    • 1
  • Ricardo Ambrósio Fock
    • 1
  1. 1.Experimental Hematology Laboratory, Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical SciencesUniversity of Sao PauloSao PauloBrazil
  2. 2.Department of Nutrition, School of Public HealthUniversity of Sao PauloSao PauloBrazil

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