Glycyrrhizin Inhibits Interleukin-8 Production and Nuclear Factor–κ B Activity in Lung Epithelial Cells, but Not Through Glucocorticoid Receptors

Takei, Hironori; Baba, Yuichiro; Hisatsune, Akinori; Katsuki, Hiroshi; Miyata, Takeshi; Yokomizo, Kazumi; Isohama, Yoichiro

Abstract This study was designed to examine the glucocorticoid-like inhibitory effect of glycyrrhizin (GL) on interleukin (IL)-8 production in A549 lung epithelial cells. GL, as well as dexamethasone (DEX) inhibited both tumor necrosis factor (TNF)-α –and IL-1β –induced IL-8 production, mRNA expression, and promoter activity in A549 cells. Both GL and DEX inhibited transactivation of nuclear factor (NF)-κ B, without inhibiting translocation of the NF-κ B p65 subunit to the nucleus. However, the effect of GL was insensitive to RU486, a GR antagonist, and to GR knockdown by siRNA. Furthermore, only GL inhibited DNA binding of p65 to the IL-8 promoter region. These findings indicated that GL had a glucocorticoid-like inhibitory effect on IL-8 production via a mechanism that differs from that of glucocorticoids.