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

Sun Hong Park; Min Sik Kyeong; Yuri Hwang; Shi Yong Ryu; Sang-Bae Han; Youngsoo Kim

doi:10.1016/j.bbrc.2012.02.091

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

Biochem Biophys Res Commun. 2012 Mar 23;419(4):735-40. doi: 10.1016/j.bbrc.2012.02.091. Epub 2012 Feb 24.

Authors

Sun Hong Park¹, Min Sik Kyeong, Yuri Hwang, Shi Yong Ryu, Sang-Bae Han, Youngsoo Kim

Affiliation

¹ College of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea.

PMID: 22387540
DOI: 10.1016/j.bbrc.2012.02.091

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Vesicular Transport / metabolism
Animals
Cytokines / metabolism*
Diet
Gene Expression / drug effects
Guaiacol / analogs & derivatives*
Guaiacol / chemistry
Guaiacol / pharmacology
Inflammation / genetics
Interferon Regulatory Factor-3 / agonists
Lipopolysaccharides / antagonists & inhibitors*
Lipopolysaccharides / immunology
Lymphocyte Antigen 96 / antagonists & inhibitors*
Lymphocyte Antigen 96 / immunology
Macrophages / drug effects
Macrophages / immunology
Mice
Myeloid Differentiation Factor 88 / metabolism
NF-kappa B / metabolism
Toll-Like Receptor 4 / metabolism*
Transcription Factor AP-1 / metabolism
Zingiber officinale / chemistry*

Substances

(10)-dehydrogingerdione
Adaptor Proteins, Vesicular Transport
Cytokines
Interferon Regulatory Factor-3
Irf3 protein, mouse
Lipopolysaccharides
Ly96 protein, mouse
Lymphocyte Antigen 96
Myeloid Differentiation Factor 88
NF-kappa B
TICAM-1 protein, mouse
Tlr4 protein, mouse
Toll-Like Receptor 4
Transcription Factor AP-1
Guaiacol