title: Luteolin inhibits hyperglycemia-induced proinflammatory cytokine production and its epigenetic mechanism in human monocytes.
abstract: 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.
authors.affiliation: Pharmacology Research Center, Korea Research Institute of Chemical Technology, Daejeon, 305-600, South Korea.
authors.forename: Hye Joo
authors.initials: HJ
authors.lastname: Kim
authors.forename: Wooje
authors.initials: W
authors.lastname: Lee
authors.forename: Jung-Mi
authors.initials: JM
authors.lastname: Yun
mesh_terms: D000107:Acetylation; D002460:Cell Line; D003470:Culture Media / Q000737:chemistry; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005947:Glucose / Q000737:chemistry*; D051548:Histone Acetyltransferases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D047311:Luteolin / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D003470:Culture Media; D006657:Histones; D007004:Hypoglycemic Agents; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D051548:Histone Acetyltransferases; D005947:Glucose; D047311:Luteolin
keywords: NF-κB; acetylation; deacetylation; luteolin; p300