P114	LXR activation induces phagocyte NADPH oxidase activity in human macrophages and inhibits Salmonella replication within these cells.
1A.Nohara, 1G.Chinetti-Gbaguidi, 1C.Fontaine, 1E.Rigamonti, 1J-C.Fruchart, 1E.Teissier, 2M.Marceau, 2M.Simonet, 1B.Staels
1UR 545 INSERM- Institut Pasteur de Lille and Faculté de Pharmacie, Université de Lille II,, Lille, FR; 2E0364 Inserm-Université de Lille II & Institut Pasteur, Lille, FR.

Macrophages play a central role in host defense against pathogen microbes due to their ability to rapidly recognize bacterial components leading to the activation of an arsenal of antimicrobial effectors to eliminate microbes. Among these, NADPH oxidase activation is an integral part of host defense leading to generation of reactive oxygen species (ROS) causing oxidative damage to bacteria. LXRs are nuclear receptors expressed in macrophages where they play a role in the control of cholesterol homeostasis and inflammation. In addition, it has been recently reported that LXRs are important for macrophage survival and play a role in the innate immune response in the mouse. In this study we investigated whether LXR control the host defense mechanisms in human macrophages. We report that LXRs activation results in ROS generation, which is attributable to the induction of NADPH oxidase. LXR agonists enhance NADPH oxidase subunits p47phox and gp91phox gene expression. The NADPH oxidase inhibitor diphenyleneiodinium (DPI) abolishes the increase in ROS production. Finally, LXR activation prevents intracellular Salmonella proliferation in human macrophages, an effect which is partially prevented by DPI. These data provide evidences for a novel potential mechanism by which LXR control the immune response in human macrophages.

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