PMID- 25088305 OWN - NLM STAT- MEDLINE DCOM- 20150413 LR - 20161125 IS - 2042-650X (Electronic) IS - 2042-6496 (Linking) VI - 5 IP - 9 DP - 2014 Sep TI - Esculetin inhibits the inflammatory response by inducing heme oxygenase-1 in cocultured macrophages and adipocytes. PG - 2371-7 LID - 10.1039/c4fo00351a [doi] AB - 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-alpha (TNF-alpha), and monocyte chemoattractant protein-1 (MCP-1) production was measured in the coculture supernatant. ECT decreased the secretion of NO, TNF-alpha, and MCP-1. The expression of adipogenic proteins, including peroxisome proliferator-activated receptors gamma (PPARgamma) and CCAAT/enhancer binding protein alpha (C/EBPalpha) 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-alpha, 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. FAU - Kim, Younghwa AU - Kim Y AD - 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. FAU - Park, Yooheon AU - Park Y FAU - Namkoong, Seulgi AU - Namkoong S FAU - Lee, Junsoo AU - Lee J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Food Funct JT - Food & function JID - 101549033 RN - 0 (CCAAT-Enhancer-Binding Protein-alpha) RN - 0 (PPAR gamma) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Umbelliferones) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - SM2XD6V944 (esculetin) SB - IM MH - 3T3-L1 Cells MH - Adipocytes/*drug effects/immunology MH - Animals MH - CCAAT-Enhancer-Binding Protein-alpha/genetics/immunology MH - Coculture Techniques MH - Heme Oxygenase-1/genetics/*immunology MH - Macrophages/*drug effects/immunology MH - Mice MH - PPAR gamma/genetics/immunology MH - Tumor Necrosis Factor-alpha/genetics/immunology MH - Umbelliferones/*pharmacology EDAT- 2014/08/05 06:00 MHDA- 2015/04/14 06:00 CRDT- 2014/08/05 06:00 PHST- 2014/08/05 06:00 [entrez] PHST- 2014/08/05 06:00 [pubmed] PHST- 2015/04/14 06:00 [medline] AID - 10.1039/c4fo00351a [doi] PST - ppublish SO - Food Funct. 2014 Sep;5(9):2371-7. doi: 10.1039/c4fo00351a.