title: Adiponectin induces TNF-alpha and IL-6 in macrophages and promotes tolerance to itself and other pro-inflammatory stimuli.
abstract: Adiponectin exerts anti-inflammatory effects via macrophages, suppressing the production of pro-inflammatory cytokines in response to bacterial lipopolysaccharide (LPS). Here, we provide experimental evidence that the "anti-inflammatory" effect of adiponectin may be due to an induction of macrophage tolerance: globular adiponectin (gAd) is a powerful inducer of TNF-alpha and IL-6 secretion in primary human peripheral macrophages, in the THP-1 human macrophage cell line, and in primary mouse peritoneal macrophages. Pre-exposure of macrophages to 10 microg/ml gAd rendered them tolerant to further gAd exposure or to other pro-inflammatory stimuli such as TLR3 ligand polyI:C and TLR4 ligand LPS, while pre-exposure to 1 microg/ml of and re-exposure to 10 microg/ml gAd unmasked its pro-inflammatory properties. GAd induced NF-kappaB activation and tolerance to further gAd or LPS exposure. Our data suggest that adiponectin constant presence in the circulation in high levels (in lean subjects) renders macrophages resistant to pro-inflammatory stimuli, including its own.
authors.affiliation: Department of Clinical Chemistry-Biochemistry, School of Medicine, University of Crete, Heraklion, Crete GR-710 03, Greece. tsatsani@med.uoc.gr
authors.forename: Christos
authors.initials: C
authors.lastname: Tsatsanis
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Zacharioudaki
authors.forename: Ariadne
authors.initials: A
authors.lastname: Androulidaki
authors.forename: Erini
authors.initials: E
authors.lastname: Dermitzaki
authors.forename: Ioannis
authors.initials: I
authors.lastname: Charalampopoulos
authors.forename: Vassilis
authors.initials: V
authors.lastname: Minas
authors.forename: Achille
authors.initials: A
authors.lastname: Gravanis
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Margioris
mesh_terms: D052242:Adiponectin; D002460:Cell Line; D016207:Cytokines / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology*; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage*; D015850:Interleukin-6 / Q000276:immunology*; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D052242:Adiponectin; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha