Adiponectin differentially regulates cytokines in porcine macrophages.
Adiponectin, an adipocyte-derived hormone, attenuates the production of TNFalpha by activated human macrophages. In the present study, we used porcine blood-derived macrophages to test the hypothesis that the anti-inflammatory action of adiponectin includes suppression of IL6 and an induction of IL10. Adiponectin suppressed both TNFalpha and IL6 production in macrophages activated with lipopolysaccharide (P<0.01). In contrast, adiponectin increased IL10 expression (P<0.05) and augmented (P<0.05) the induction of this cytokine by lipopolysaccharide (LPS). Mechanistically, the attenuation of proinflammatory cytokine production by adiponectin was associated with an attenuation of the translocation of NFkappaB to the nucleus. Either adiponectin or inhibition of ERK1/2 with U0126 diminished the induction of IL6 by LPS (P<0.05), but the combination of adiponectin and the inhibitor did not further reduce IL6 production. In contrast, the inhibitory actions of adiponectin and a p38 MAPK inhibitor (SB203580) were additive (P<0.05). These data indicate that the anti-inflammatory actions of adiponectin include suppression of IL6 and induction of IL10. In addition, we provide evidence that some of the anti-inflammatory actions of adiponectin are mediated in part by suppression of NFkappaB signaling and ERK1/2 activity.
Wulster-Radcliffe
Meghan C
MC
Department of Animal Sciences, Comparative Medicine Program, Purdue University, West Lafayette, IN, USA.
Ajuwon
Kolapo M
KM
Wang
Jiazhen
J
Christian
John A
JA
Spurlock
Michael E
ME
D021581:Active Transport, Cell Nucleus; D052242:Adiponectin; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002070:Butadienes / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D007093:Imidazoles / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D016753:Interleukin-10 / Q000096:biosynthesis / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013552:Swine; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases
D052242:Adiponectin; D000893:Anti-Inflammatory Agents; D002070:Butadienes; D016207:Cytokines; D004791:Enzyme Inhibitors; D007093:Imidazoles; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009570:Nitriles; D011506:Proteins; D011725:Pyridines; D012333:RNA, Messenger; C113580:U 0126; D016753:Interleukin-10; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580