title: Inhibition of LPS binding to MD-2 co-receptor for suppressing TLR4-mediated expression of inflammatory cytokine by 1-dehydro-10-gingerdione from dietary ginger.
abstract: Myeloid differentiation protein 2 (MD-2) is a co-receptor of toll-like receptor 4 (TLR4) for innate immunity. Here, we delineated a new mechanism of 1-dehydro-10-gingerdione (1D10G), one of pungent isolates from ginger (Zingiber officinale), in the suppression of lipopolysaccharide (LPS)-induced gene expression of inflammatory cytokines. 1D10G inhibited LPS binding to MD-2 with higher affinity than gingerol and shogaol from dietary ginger. Moreover, 1D10G down-regulated TLR4-mediated expression of nuclear factor-κB (NF-κB) or activating protein 1 (AP1)-target genes such as tumor necrosis factor α (TNF-α) and interleukin-1β, as well as those of interferon (IFN) regulatory factor 3 (IRF3)-target IFN-β gene and IFN-γ inducible protein 10 (IP-10) in LPS-activated macrophages. Taken together, MD-2 is a molecular target in the anti-inflammatory action of 1D10G.
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors.forename: Sun Hong
authors.initials: SH
authors.lastname: Park
authors.forename: Min Sik
authors.initials: MS
authors.lastname: Kyeong
authors.forename: Yuri
authors.initials: Y
authors.lastname: Hwang
authors.forename: Shi Yong
authors.initials: SY
authors.lastname: Ryu
authors.forename: Sang-Bae
authors.initials: SB
authors.lastname: Han
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D004032:Diet; D015870:Gene Expression / Q000187:drug effects; D020939:Zingiber officinale / Q000737:chemistry*; D006139:Guaiacol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D007249:Inflammation / Q000235:genetics; D050838:Interferon Regulatory Factor-3 / Q000819:agonists; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000276:immunology; D051218:Lymphocyte Antigen 96 / Q000037:antagonists & inhibitors* / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D016207:Cytokines; D006139:Guaiacol; D050838:Interferon Regulatory Factor-3; D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D018808:Transcription Factor AP-1; C561631:(10)-dehydrogingerdione; C494233:Irf3 protein, mouse; C411728:Ly96 protein, mouse; C476286:Ticam1 protein, mouse; C493487:Tlr4 protein, mouse