Luteolin Inhibits Hyperglycemia‐Induced Proinflammatory Cytokine Production and Its Epigenetic Mechanism in Human Monocytes

• Published in: Phytotherapy research 2014-09, Vol.28 (9), p.1383-1391
• Main Authors: Kim, Hye Joo, Lee, Wooje, Yun, Jung‐Mi
• Format: Article
• Language: English
• Subjects: Acetylation; antioxidants; celery; Cell Line; chamomile; Culture Media - chemistry; cultured cells; deacetylation; diabetic complications; E1A-Associated p300 Protein - metabolism; Epigenesis, Genetic - drug effects; epigenetics; gene expression; glucose; Glucose - chemistry; Histone Acetyltransferases - metabolism; histones; Histones - metabolism; Humans; hyperglycemia; Hyperglycemia - metabolism; Hypoglycemic Agents - pharmacology; Interleukin-6 - metabolism; leaves; luteolin; Luteolin - pharmacology; mannitol; monocytes; Monocytes - drug effects; NF-kappa B - metabolism; NF-κB; p300; Perilla; Promoter Regions, Genetic; secretion; Signal Transduction - drug effects; sweet peppers; tea; transcription factor NF-kappa B; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0951-418X; 1099-1573
• DOI: 10.1002/ptr.5141

Hyperglycemia is a key feature in diabetes. Hyperglycemia has been implicated as a major contributor to several complications of diabetes. High glucose levels induce the release of proinflammatory cytokines. Luteolin is a flavone isolated from celery, green pepper, perilla leaf, and chamomile tea. Luteolin has been reported to possess antimutagenic, antitumorigenic, antioxidant, and anti‐inflammatory properties. In this study, we investigated the effects of luteolin on proinflammatory cytokine secretion and its underlying epigenetic regulation in high‐glucose‐induced human monocytes. Human monocytic (THP‐1) cells were cultured under controlled (14.5 mM mannitol), normoglycemic (NG, 5.5 mM glucose), or hyperglycemic (HG, 20 mM glucose) conditions, in the absence or presence of luteolin. Luteolin (3–10 μM) was added for 48 h. While hyperglycemic conditions significantly induced histone acetylation, NF‐κB activation, and proinflammatory cytokine (IL‐6 and TNF‐α) release from THP‐1 cells, luteolin suppressed NF‐κB activity and cytokine release. Luteolin also significantly reduced CREB‐binding protein/p300 (CBP/p300) gene expression, as well as the levels of acetylation and histone acetyltransferase (HAT) activity of the CBP/p300 protein, which is a known NF‐κB coactivator. These results suggest that luteolin inhibits HG‐induced cytokine production in monocytes, through epigenetic changes involving NF‐κB. We therefore suggest that luteolin may be a potential candidate for the treatment and prevention of diabetes and its complications. Copyright © 2014 John Wiley & Sons, Ltd.