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-1 beta, TNF-alpha, and IFN-alpha/beta, enhanced antigen capture capacity, inhibited migration to SDF-1 alpha and MIP-3 beta, 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 I kappa B alpha/beta nuclear translocation of NF-kappa B 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-kappa B and MAPK signalings. (C) 2010 Elsevier B.V. All rights reserved.