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-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).
Yamaguchi
Noboru
N
Department of Preventive Dentistry, Kyushu University Faculty of Dental Science, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Argueta
Jose Guillermo Martinez
JG
Masuhiro
Yoshikazu
Y
Kagishita
Maki
M
Nonaka
Kazuaki
K
Saito
Toshiyuki
T
Hanazawa
Shigemasa
S
Yamashita
Yoshihisa
Y
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
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