Tollip Regulates Proinflammatory Responses to Interleukin-1 and Lipopolysaccharide

Didierlaurent, Arnaud; Brissoni, Brian; Velin, Dominique; Aebi, Natalia; Tardivel, Aubry; Käslin, Edgar; Sirard, Jean Claude; Angelov, Georgi; Tschopp, Jürg; Burns, Kimberly

doi:10.1128/mcb.26.3.735-742.2006

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Journal article

Tollip Regulates Proinflammatory Responses to Interleukin-1 and Lipopolysaccharide

Didierlaurent, Arnaud Department of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland
Brissoni, Brian Department of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland
Velin, Dominique Department of Gastroenterology, CHUV, BH 18-521, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland
Aebi, Natalia Department of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland
Tardivel, Aubry Department of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland
Käslin, Edgar Department of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland
Sirard, Jean Claude INSERM, E0364, Institut de Biologie-Institut Pasteur de Lille, 1 Rue du Pr Calmette, 59021 Lille, France
Angelov, Georgi Ludwig Institute for Cancer Research, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland
Tschopp, Jürg Department of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland
Burns, Kimberly Department of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland

Published in:

Molecular and Cellular Biology. - American Society for Microbiology. - 2006, vol. 26, no. 3, p. 735-742

English ABSTRACT
Activation of interleukin-1 (IL-1) receptor (IL-1R), Toll-like receptor 2 (TLR2), and TLR4 triggers NF-κB and mitogen-activated protein kinase (MAPK)-dependent signaling, thereby initiating immune responses. Tollip has been implicated as a negative regulator of NF-κB signaling triggered by these receptors in in vitro studies. Here, deficient mice were used to determine the physiological contribution of Tollip to immunity. NF-κB, as well as MAPK, signaling appeared normal in Tollip-deficient cells stimulated with IL-1β or the TLR4 ligand lipopolysaccharide (LPS). Similarly, IL-1β- and TLR-driven activation of dendritic cells and lymphocytes was indistinguishable from wild-type cells. In contrast, the production of the proinflammatory cytokines, IL-6 and tumor necrosis factor alpha was significantly reduced after IL-1β and LPS treatment at low doses but not at lethal doses of LPS. Tollip therefore controls the magnitude of inflammatory cytokine production in response to IL-1β and LPS.

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