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

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 I kappa B alpha 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 I kappa B alpha/nuclear factor-kappa B 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.