Inhibition of bone marrow-derived dendritic cell maturation by glabridin.
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.
Kim
Jee Youn
JY
College of Pharmacy and Medical Research Center (CICT), Chungbuk National University, 410 Seongbong, Heungduk, Cheongju, Chungbuk 361-763, Republic of Korea.
Kang
Jong Soon
JS
Kim
Hwan Mook
HM
Ryu
Hwa Sun
HS
Kim
Hyung Sook
HS
Lee
Hong Kyung
HK
Kim
Yeon Jin
YJ
Hong
Jin Tae
JT
Kim
Youngsoo
Y
Han
Sang-Bae
SB
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
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