Visit our Expo - Redox and Inflammation signaling 2012

VIII. Inflammation specific signaling Poster VIII, 10
Mitochondrial uncoupling protein UCP2 regulates the LPS-induced ROS signaling in
innate imunity.
Yalin Emre, Corinne Hurtaud, Tobias Nübel, François Criscuolo, Daniel Ricquier, and
Anne-Marie Cassard-Doulcier
CNRS-UPR 9078, Faculté de Médecine Paris 5 Necker-Enfants Malades, 156 rue de
Vaugirard, 75730 Paris Cedex 15, France. E-mail : emre@necker.fr,
hurtaud@necker.fr, nuebel@necker.fr, criscuolo@wanadoo.fr, ricquier@necker.fr and
cassard-doulcier@necker.fr
Macrophages constitute the first line of defense against pathogens in innate immunity. The
recognition by Toll-like receptor-4 (TLR4) of lipopolysaccharides (LPS), a chief pathogenassociated
molecular pattern of Gram negative bacteria, triggers innate activation of
macrophages. Efficient activation is largely dependent upon the concomitant reactive oxygen
species (ROS) signaling. Since mitochondria is the main site of ROS production in resting
cells and the inner mitochondrial membrane protein UCP2 (uncoupling protein 2) is a
negative regulator of mitochondrial ROS production, we investigated a possible involvement
of UCP2 in macrophage innate activation and more precisely in the underlying ROS
signaling. We showed that UCP2 was quickly downregulated in macrophages in response to
LPS in order to increase the mitochondrial ROS production thus promoting MAPK
phosphorylation and activation. Consistent with this, UCP2-deficient macrophages have
increased nitric oxide production, cytokine release and their ablity to migrate. Based on our
data we conclude that the mitochondrial UCP2 plays an important role in pathogen-mediated
innate activation of macrophages by negatively regulating the LPS-induced ROS signaling.
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