title: Esculetin inhibits the inflammatory response by inducing heme oxygenase-1 in cocultured macrophages and adipocytes.
abstract: Obesity is associated with chronic low-grade inflammation of adipose tissue. In this study, we investigated the anti-inflammatory effects of esculetin (ECT) through up-regulation of heme oxygenase-1 (HO-1) in cocultured macrophages and adipocytes. RAW264.7 macrophages and differentiated 3T3-L1 adipocytes were cocultured in serum-free Dulbecco's modified Eagle's medium with or without ECT for 24 h. Nitric oxide (NO), tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) production was measured in the coculture supernatant. ECT decreased the secretion of NO, TNF-α, and MCP-1. The expression of adipogenic proteins, including peroxisome proliferator-activated receptors γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα) in cocultured adipocytes and inducible nitric oxide synthase (iNOS) in cocultured macrophages, was inhibited by ECT. Additionally, HO-1 expression was induced in cocultured macrophages and adipocytes. Silencing of HO-1 expression increased the production of NO, TNF-α, and MCP-1 in cocultured cells, in spite of the presence of ECT. This study demonstrated that ECT exhibited anti-inflammatory properties by inhibiting the production of proinflammatory cytokines in the interaction between adipocytes and macrophages through HO-1 expression. ECT may have the potential to improve chronic inflammation in obesity.
authors.affiliation: Department of Food Science and Technology, College of Agriculture, Life and Environment Sciences, Chungbuk National University, 52 Naesudong-ro, Heungdeok-gu, Cheongju, Chungbuk 361-763, Korea. junsoo@chungbuk.ac.kr.
authors.forename: Younghwa
authors.initials: Y
authors.lastname: Kim
authors.forename: Yooheon
authors.initials: Y
authors.lastname: Park
authors.forename: Seulgi
authors.initials: S
authors.lastname: Namkoong
authors.forename: Junsoo
authors.initials: J
authors.lastname: Lee
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000276:immunology; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000276:immunology; D018920:Coculture Techniques; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D047495:PPAR gamma / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D014468:Umbelliferones / Q000494:pharmacology*
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D047495:PPAR gamma; D014409:Tumor Necrosis Factor-alpha; D014468:Umbelliferones; D051547:Heme Oxygenase-1; C007628:esculetin