title: Inhibition of bone marrow-derived dendritic cell maturation by glabridin.
abstract: Glabridin has multiple pharmacological activities including anti-microbial, anti-atherosclerotic, anti-nephritic, anti-inflammatory and cardiovascular protective activities. In this study, we investigated the effect of glabridin on dendritic cells, which play an essential role in innate and adaptive immune responses. Glabridin inhibited lipopolysaccharide-, poly (I:C)-, or zymosan-induced phenotypic maturation of dendritic cells (DCs), as proven by the decreased expression of CD40, CD80, CD86, MHC-I, and MHC-II. Glabridin decreased the functional maturation of DCs, in that glabridin attenuated pro-inflammatory cytokine production of IL-12, IL-1β, TNF-α, and IFN-α/β, enhanced antigen capture capacity, inhibited migration to SDF-1α and MIP-3β, and impaired induction of allogenic T cell activation. We also showed that glabridin inhibited zymosan-induced inflammation in mice. As a mode of action, we showed that glabridin inhibited degradation of IκΒα/β, nuclear translocation of NF-κB p65/p50, and phosphorylation of ERK, JNK, and p38 MAPKs. Taken together, the present results show that glabridin inhibits dendritic cell maturation by blocking NF-κB and MAPK signalings.
authors.affiliation: College of Pharmacy and Medical Research Center (CICT), Chungbuk National University, 410 Seongbong, Heungduk, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Jee Youn
authors.initials: JY
authors.lastname: Kim
authors.forename: Jong Soon
authors.initials: JS
authors.lastname: Kang
authors.forename: Hwan Mook
authors.initials: HM
authors.lastname: Kim
authors.forename: Hwa Sun
authors.initials: HS
authors.lastname: Ryu
authors.forename: Hyung Sook
authors.initials: HS
authors.lastname: Kim
authors.forename: Hong Kyung
authors.initials: HK
authors.lastname: Lee
authors.forename: Yeon Jin
authors.initials: YJ
authors.lastname: Kim
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.forename: Sang-Bae
authors.initials: SB
authors.lastname: Han
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000166:cytology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D007372:Interferons / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D007378:Interleukins; D007529:Isoflavones; D016328:NF-kappa B; D010636:Phenols; D014409:Tumor Necrosis Factor-alpha; D007372:Interferons; D020929:Mitogen-Activated Protein Kinase Kinases; C107601:glabridin