Adiponectin inhibits Toll-like receptor family-induced signaling

Recent studies have shown that adiponectin, an adipocyte-derived cytokine, acts as a potent inhibitor of inflammatory responses. It has been also demonstrated that bacterial and viral signalings in host cells are triggered via Toll-like receptor (TLR) molecules. Therefore, in the present study, we investigated whether globular adiponectin (gAd) would be able to inhibit TLR-mediated nuclear factor-kappa B (NF-kappa B) signaling in mouse macrophages (RAW264). gAd predominantly bound to the Adi-poR1 receptor and suppressed TLR-mediated NF-kappa B signaling. gAd-mediated inhibition of TLR-mediated I kappa B phosphorylation and NF-kappa B activation was eliminated by the pretreatment of cycloheximide. Also their inhibitions of gAd were blocked by preincubation of the cells with an antibody against Adipo-R1, but not with an antibody against AdipoR2. Taken together, these findings indicate that adiponectin negatively regulates macrophage-like cell response to TLR ligands via an unknown endogenous product(s). (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.