Selenium is a micronutrient essential for human health. Selenium supplementation has been reported to lower mortality from colon cancer[1, 2]. Selenium is present in selenoproteins including glutathione peroxidases (GPx) 1-4. GPxs are antioxidant enzymes that protect cells from excessive oxidative stress. Knock-out of GPx1 and 2 leads to increased sensitivity to bacterial-induced inflammation in the gut suggesting they may have a role in maintaining innate immunity homeostasis against inflammatory stimulation from exposure to luminal bacteria. GPx4 has been linked to leukotriene metabolism [3, 4]. The aim of the present work was to examine the role of selenium and GPxs in the gastrointestinal cell line Caco-2 in relation to inflammatory stimulation. To assess inflammatory signalling, a luciferase reporter cell model was developed in Caco-2 cells, in which luciferase expression was under the control regulatory elements that bound the Nuclear Factor-kappa B, the core inflammatory transcription factor[5]. As a control reporter luciferase coding sequences were linked to a TATA box. Using cells expressing these constructs the impact of GPx4 knockdown on Nuclear Factor-kappa B activation by endogenous (TNFα) and exogenous(bacterial flagellin) inflammatory stimuli was investigated. Using small interfering RNA GPx4 expression was knocked down by approximately 80% as assessed by RTPCR and Western blotting. Knock-down had no effect on activation of luciferase activity by either stimulus. However, when cells were grown in Se deficient conditions a 30% increase in TNFα-induced reporter activity was observed. Future work will address how other GPxs and selenium modulate Nuclear Factor-kappa B signaling in intestinal epithelial cells (and thus protect gut cells from inflammation) and the possible importance of radical oxygen species in this mechanism.