Didierlaurent, Arnaud Brissoni, Brian Velin, Dominique Aebi, Natalia Tardivel, Aubry Käslin, Edgar Sirard, Jean Claude Angelov, Georgi Tschopp, Jürg Burns, Kimberly <jats:title>ABSTRACT</jats:title> <jats:p>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.</jats:p> application/pdf https://sonar.ch/global/documents/261769 eng info:eu-repo/semantics/altIdentifier/doi/10.1128/mcb.26.3.735-742.2006 info:eu-repo/semantics/altIdentifier/issn/0270-7306 info:eu-repo/semantics/openAccess Molecular and Cellular Biology. - American Society for Microbiology. - 2006, vol. 26, no. 3, p. 735-742 Cell Biology Molecular Biology Tollip Regulates Proinflammatory Responses to Interleukin-1 and Lipopolysaccharide http://purl.org/coar/resource_type/c_6501