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Differential effects of selenium and knock-down of glutathione peroxidases on TNF alpha and flagellin inflammatory responses in gut epithelial cells

Lookup NU author(s): Guanyu Gong, Dr Catherine Meplan, Dr Hannah Gautrey, Dr Judith HallORCiD, Professor John Hesketh

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Abstract

Selenium (Se) is essential for human health. Despite evidence that Se intake affects inflammatory responses, the mechanisms by which Se and the selenoproteins modulate inflammatory signalling, especially in the gut, are not yet defined. The aim of this work was to assess effects of altered Se supply and knock-down of individual selenoproteins on NF-kappa B activation in gut epithelial cells. Caco-2 cells were stably transfected with gene constructs expressing luciferase linked either to three upstream NF-kappa B response elements and a TATA box or only a TATA box. TNF alpha and flagellin activated NF-kappa B-dependent luciferase activity and increased IL-8 expression. Se depletion decreased expression of glutathione peroxidase1 (GPX1) and selenoproteins H and W and increased TNF alpha-stimulated luciferase activity, endogenous IL-8 expression and reactive oxygen species (ROS) production. These effects were not mimicked by independent knock-down of either GPX1, selenoprotein H or W; indeed, GPX1 knock-down lowered TNF alpha-induced NF-kappa B activation and did not affect ROS levels. GPX4 knock-down decreased NF-kappa B activation by flagellin but not by TNF alpha. We hypothesise that Se depletion alters the pattern of expression of multiple selenoproteins that in turn increases ROS and modulates NF-kappa B activation in epithelial cells, but that the effect of GPX1 knock-down is ROS-independent.

Publication metadata

Author(s): Gong G, Meplan C, Gautrey H, Hall J, Hesketh JE

Publication type: Article

Publication status: Published

Journal: Genes & Nutrition

Year: 2012

Volume: 7

Issue: 2

Pages: 167-178

Print publication date: 01/04/2012

ISSN (print): 1555-8932

ISSN (electronic): 1865-3499

Publisher: Springer

URL: http://dx.doi.org/10.1007/s12263-011-0256-4

DOI: 10.1007/s12263-011-0256-4

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