title: Adiponectin inhibits Toll-like receptor family-induced signaling.
abstract: 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-kappaB (NF-kappaB) signaling in mouse macrophages (RAW264). gAd predominantly bound to the AdipoR1 receptor and suppressed TLR-mediated NF-kappaB signaling. gAd-mediated inhibition of TLR-mediated IkappaB phosphorylation and NF-kappaB activation was eliminated by the pretreatment of cycloheximide. Also their inhibitions of gAd were blocked by preincubation of the cells with an antibody against AdipoR1, 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).
authors.affiliation: Department of Preventive Dentistry, Kyushu University Faculty of Dental Science, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Yamaguchi
authors.forename: Jose Guillermo Martinez
authors.initials: JG
authors.lastname: Argueta
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Masuhiro
authors.forename: Maki
authors.initials: M
authors.lastname: Kagishita
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nonaka
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Saito
authors.forename: Shigemasa
authors.initials: S
authors.lastname: Hanazawa
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Yamashita
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects; D052242:Adiponectin / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D019921:Biotinylation; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D017930:Genes, Reporter; D005982:Glutathione Transferase / Q000378:metabolism; D051550:I-kappa B Kinase / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D016328:NF-kappa B; D011500:Protein Synthesis Inhibitors; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; C475419:adiponectin receptor 1, mouse; C475421:adiponectin receptor 2, mouse; D003513:Cycloheximide; D008156:Luciferases; D005982:Glutathione Transferase; D051550:I-kappa B Kinase