title: Apigenin inhibits the expression of IL-6, IL-8, and ICAM-1 in DEHP-stimulated human umbilical vein endothelial cells and in vivo.
abstract: Di-(2-ethylhexyl) phthalate (DEHP) in house dust is associated with asthma and allergic inflammatory symptoms in children. This study aimed to examine an inhibitory effect of a flavonoid apigenin on DEHP-stimulated inflammatory responses in human umbilical vein endothelial cells (HUVECs). We found that apigenin significantly suppressed DEHP-stimulated expression of intercellular adhesion molecule-1 (ICAM-1) at the mRNA and protein levels and subsequently inhibited the adhesion of THP-1 monocytic cells to HUVECs. Treatment with apigenin also led to a dose-dependent inhibition of mRNA and protein expression of interleukin (IL)-6 and IL-8 in DEHP-stimulated HUVECs. Moreover, pretreatment with apigenin partially inhibited the DEHP-induced activation of c-Jun N-terminal kinase (JNK) but not the degradation of IκBα or the phosphorylation of extracellular-regulated kinase (ERK)1/2, indicating that the inhibitory effect of apigenin on the expression of IL-6, IL-8, and ICAM-1 may be mediated by JNK pathway but not IκBα/nuclear factor-κB or ERK/mitogen-activated protein kinase pathway. Furthermore, apigenin reduced the release of IL-6, IL-8, and ICAM-1 and inhibited compound 48/80-induced systemic anaphylaxis in vivo. These results suggest that apigenin can be used as a therapeutic means for the treatment of DEHP-associated allergic disorders.
authors.affiliation: Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, Fujian Province, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Liao
authors.forename: Jianglin
authors.initials: J
authors.lastname: Fan
authors.forename: Ting
authors.initials: T
authors.lastname: Ye
authors.forename: Xia
authors.initials: X
authors.lastname: Sun
authors.forename: Sijun
authors.initials: S
authors.lastname: Dong
mesh_terms: D000707:Anaphylaxis / Q000188:drug therapy; D000818:Animals; D047310:Apigenin / Q000494:pharmacology*; D002478:Cells, Cultured; D004051:Diethylhexyl Phthalate / Q000276:immunology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D003189:p-Methoxy-N-methylphenethylamine; D047310:Apigenin; D004051:Diethylhexyl Phthalate; D051550:I-kappa B Kinase; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases