title: Glycyrrhizin inhibits interleukin-8 production and nuclear factor-kappaB activity in lung epithelial cells, but not through glucocorticoid receptors.
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)-alpha- and IL-1beta-induced IL-8 production, mRNA expression, and promoter activity in A549 cells. Both GL and DEX inhibited transactivation of nuclear factor (NF)-kappaB, without inhibiting translocation of the NF-kappaB 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.
authors.affiliation: Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Takei
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Baba
authors.forename: Akinori
authors.initials: A
authors.lastname: Hisatsune
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katsuki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyata
authors.forename: Kazumi
authors.initials: K
authors.lastname: Yokomizo
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Isohama
mesh_terms: D021581:Active Transport, Cell Nucleus; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008168:Lung; D011401:Promoter Regions, Genetic; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000502:physiology; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D016209:Interleukin-8; D011965:Receptors, Glucocorticoid; D051996:Transcription Factor RelA; D019695:Glycyrrhizic Acid; D004247:DNA