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Effects of Protein-Energy Malnutrition on NF-KappaB Signalling in Murine Peritoneal Macrophages

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Abstract

Protein-energy malnutrition (PEM) is an important public health problem affecting millions of people worldwide. PEM decreases resistance to infection, impairing a number of physiological processes. In unstimulated cells, NF-κB is kept from binding to its consensus sequence by the inhibitor IκBα, which retains NF-κB in the cytoplasm. Upon various signals, such as lipopolysaccharide (LPS), IκBα is rapidly degraded and NF-κB is induced to translocate into the nucleus, where it activates expression of various genes that participate in the inflammatory response, including those involved in the synthesis of TNF-α. TRAF-6 is a cytoplasmic adapter protein that links the stimulatory signal from Toll like receptor-4 to NF-κB. The aim of this study was to evaluate the effect of malnutrition on induction of TNF-α by LPS in murine peritoneal macrophages. We evaluated peritoneal cellularity, the expression of MyD88, TRAF-6, IKK, IκBα and NF-κB, NF-κB activation and TNF-α mRNA and protein synthesis in macrophages. Two-month-old male BALB/C mice were submitted to PEM with a low-protein diet that contained 2% protein, compared to 12% protein in the control diet. When the experimental group had lost about 20% of the original body weight, it was used in the subsequent experiments. Malnourished animals presented anemia, leucopenia and severe reduction in peritoneal cavity cellularity. TNF-α mRNA and protein levels of macrophages stimulated with LPS were significantly lower in malnourished animals. PEM also decreased TRAF-6 expression and NF-κB activation after LPS stimulation. These results led us to conclude that PEM changes NF-kB signalling pathway in macrophages to LPS stimulus.

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Acknowledgements

This investigation was supported by grants from the Fundação de Amparo a Pesquisa do Estado de São Paulo - FAPESP, Brazil.

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Authors and Affiliations

  1. Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, São Paulo University, 05508-900, São Paulo, SP, Brazil

    Ricardo Ambrósio Fock & Primavera Borelli

  2. Department of Nutrition, School of Public Health, São Paulo University, 01246-904, São Paulo, SP, Brazil

    Marcelo Macedo Rogero & Maria Carolina Borges

  3. Department of Physiology and Biophysics, Institute of Biomedical Sciences, São Paulo University, 05508-900, São Paulo, SP, Brazil

    Marco Aurélio Ramirez Vinolo & Rui Curi

  4. Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Avenida Prof. Lineu Prestes, 580, São Paulo, SP, 05508-900, Brazil

    Ricardo Ambrósio Fock

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  1. Ricardo Ambrósio Fock
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Correspondence to Ricardo Ambrósio Fock.

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Fock, R.A., Rogero, M.M., Vinolo, M.A.R. et al. Effects of Protein-Energy Malnutrition on NF-KappaB Signalling in Murine Peritoneal Macrophages. Inflammation 33, 101–109 (2010). https://doi.org/10.1007/s10753-009-9163-x

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