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Modulation of the nuclear factor-kappa B (NF-κB) signalling pathway by glutamine in peritoneal macrophages of a murine model of protein malnutrition.
MedLine Citation:
PMID:  22923035     Owner:  NLM     Status:  Publisher    
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.
Fabiana da Silva Lima; Marcelo Macedo Rogero; Mayara Caldas Ramos; Primavera Borelli; Ricardo Ambrósio Fock
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-26
Journal Detail:
Title:  European journal of nutrition     Volume:  -     ISSN:  1436-6215     ISO Abbreviation:  Eur J Nutr     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100888704     Medline TA:  Eur J Nutr     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Experimental Hematology Laboratory, Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Avenida Lineu Prestes, 580 Bloco 17, Sao Paulo, SP, 05508-900, Brazil.
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