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Apigenin Inhibits the Expression of IL-6, IL-8, and ICAM-1 in DEHP-Stimulated Human Umbilical Vein Endothelial Cells and In Vivo

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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.

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ACKNOWLEDGMENTS

We thank Professor Ryoiti Kiyama (National Institute of Advanced Industrial Science and Technology, Ibaraki, Japan) for correcting the manuscript and Dr. Tingdong Yan (National University of Singapore) for technical assistance. This investigation was supported by 100 Talents Program of Chinese Academy of Sciences (KZCX2-YW-BR-18) and the Science and Technology Planning Project of Xiamen City (3502Z20112019).

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Authors and Affiliations

  1. Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, Fujian Province, People’s Republic of China

    Jia Wang, Yanyan Liao, Ting Ye, Xia Sun & Sijun Dong

  2. Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, 409-3898, Japan

    Jianglin Fan

  3. Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, Fujian Province, People’s Republic of China

    Sijun Dong

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  1. Jia Wang
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Correspondence to Sijun Dong.

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Wang, J., Liao, Y., Fan, J. et al. Apigenin Inhibits the Expression of IL-6, IL-8, and ICAM-1 in DEHP-Stimulated Human Umbilical Vein Endothelial Cells and In Vivo . Inflammation 35, 1466–1476 (2012). https://doi.org/10.1007/s10753-012-9460-7

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