Chemokine induction by the adipocyte-derived cytokine adiponectin.
Adiponectin is an adipocyte-derived cytokine that plays a role in metabolic disorders such as obesity and diabetes mellitus. Recent work suggests that adiponectin may also affect the immune response, primarily acting as an anti-inflammatory factor. Given our observation that plasma and urine adiponectin levels are increased in SLE patients with inflammatory glomerulonephritis, we evaluated the effect of adiponectin on proinflammatory chemokines relevant to the pathogenesis of SLE nephritis. It was postulated that adiponectin would attenuate cytokine-induced chemokine expression. Cultured human microvascular endothelial cells and monocytes were treated with adiponectin, and IL-8 and MCP-1 levels were measured in the cell-culture supernatants by ELISA. Unexpectedly, full-length adiponectin significantly increased IL-8 and MCP-1 production, and did not abrogate cytokine-induced chemokine expression. Furthermore, adiponectin activated the proinflammatory transcription factor NF-kappaB. Chemokine induction by adiponectin was not mediated by the well-characterized adiponectin receptors involved in metabolic signaling, suggesting a novel receptor may be responsible for the inflammatory effect. We conclude that adiponectin may have pro- and anti-inflammatory effects, and its exact role in specific inflammatory diseases remains to be worked out.
Rovin
Brad H
BH
The Ohio State University College of Medicine and Public Health, Columbus, OH 43210, USA. rovin.1@osu.edu
Song
Huijuan
H
D052242:Adiponectin / Q000494:pharmacology; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000276:immunology; D024202:Electrophoretic Mobility Shift Assay; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015151:Immunoblotting; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000276:immunology; D050527:Mesangial Cells / Q000187:drug effects / Q000276:immunology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology; D009687:Nuclear Proteins / Q000276:immunology
C499918:ADIPOQ protein, human; D052242:Adiponectin; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016209:Interleukin-8; D016328:NF-kappa B; D009687:Nuclear Proteins