The flavone eupatilin inhibits eotaxin expression in an NF-κB-dependent and STAT6-independent manner.

The CC chemokine eotaxin contributes to epithelium-induced inflammation in airway diseases such as asthma. Eupatilin (5,7-dihydroxy-3',4',6'-trimethoxyflavone), a bioactive component of Artemisia asiatica Nakai (Asteraceae), is reported to inhibit the adhesion of eosinophils to bronchial epithelial cells. However, little is known about the molecular mechanism of eupatilin-induced attenuation of bronchial epithelium-induced inflammation. In this study, we investigated the effect of eupatilin on expression of eotaxin-1 (CCL11), a potent chemoattractant for eosinophils. Eupatilin significantly inhibited eotaxin expression in bronchial epithelial cells stimulated with TNF-α, while NF-κB and IκBα kinase (IKK) activities declined concurrently. Eupatilin also inhibited mitogen-activated protein kinase (MAPK) activity; however, all of these anti-inflammatory activities were reversed by MAPK overexpression. In contrast, eupatilin did not affect the signal transducer and activator of transcription 6 (STAT6) signalling in bronchial epithelial cells stimulated with IL-4. Furthermore, eupatilin significantly attenuated TNF-α-induced eosinophil migration. These results suggest that the eupatilin inhibits the signalling of MAPK, IKK, NF-κB and eotaxin-1 in bronchial epithelial cells, leading to inhibition of eosinophil migration.