Reference - Detail
| RRC ID | 43729 |
|---|---|
| Author | Honda H, Nagai Y, Matsunaga T, Saitoh S, Akashi-Takamura S, Hayashi H, Fujii I, Miyake K, Muraguchi A, Takatsu K. |
| Title | Glycyrrhizin and isoliquiritigenin suppress the LPS sensor toll-like receptor 4/MD-2 complex signaling in a different manner. |
| Journal | J Leukoc Biol |
| Abstract |
Recent evidences suggest that the extracts of plant products are able to modulate innate immune responses. A saponin GL and a chalcone ILG are representative components of Glycyrrhiza uralensis, which attenuate inflammatory responses mediated by TLRs. Here, we show that GL and ILG suppress different steps of the LPS sensor TLR4/MD-2 complex signaling at the receptor level. Extract of G. uralensis suppressed IL-6 and TNF-α production induced by lipid A moiety of LPS in RAW264.7 cells. Among various G. uralensis-related components of saponins and flavanones/chalcones, GL and ILG could suppress IL-6 production induced by lipid A in dose-dependent manners in RAW264.7 cells. Furthermore, elevation of plasma TNF-α in LPS-injected mice was attenuated by passive administration of GL or ILG. GL and ILG inhibited lipid A-induced NF-κB activation in Ba/F3 cells expressing TLR4/MD-2 and CD14 and BMMs. These components also inhibited activation of MAPKs, including JNK, p38, and ERK in BMMs. In addition, GL and ILG inhibited NF-κB activation and IL-6 production induced by paclitaxel, a nonbacterial TLR4 ligand. Interestingly, GL attenuated the formation of the LPS-TLR4/MD-2 complexes, resulting in inhibition of homodimerization of TLR4. Although ILG did not affect LPS binding to TLR4/MD-2, it could inhibit LPS-induced TLR4 homodimerization. These results imply that GL and ILG modulate the TLR4/MD-2 complex at the receptor level, leading to suppress LPS-induced activation of signaling cascades and cytokine production, but their effects are exerted at different steps of TLR4/MD-2 signaling. |
| Volume | 91(6) |
| Pages | 967-76 |
| Published | 2012-6-1 |
| DOI | 10.1189/jlb.0112038 |
| PII | jlb.0112038 |
| PMID | 22422925 |
| MeSH | Animals Anti-Inflammatory Agents / chemistry Anti-Inflammatory Agents / pharmacology* Cell Line Chalcones / chemistry Chalcones / pharmacology* Enzyme Inhibitors / chemistry Enzyme Inhibitors / pharmacology* Glycyrrhiza uralensis / chemistry Glycyrrhizic Acid / chemistry Glycyrrhizic Acid / pharmacology* Interleukin-6 / immunology Interleukin-6 / metabolism Lipopolysaccharide Receptors / immunology Lipopolysaccharide Receptors / metabolism Lipopolysaccharides / pharmacology* Lymphocyte Antigen 96 / immunology* Lymphocyte Antigen 96 / metabolism MAP Kinase Signaling System / drug effects* MAP Kinase Signaling System / immunology Mice Mice, Inbred BALB C Mitogen-Activated Protein Kinase Kinases / immunology Mitogen-Activated Protein Kinase Kinases / metabolism NF-kappa B / immunology NF-kappa B / metabolism Protein Multimerization / drug effects Protein Multimerization / immunology Toll-Like Receptor 4 / immunology* Toll-Like Receptor 4 / metabolism Tumor Necrosis Factor-alpha / immunology Tumor Necrosis Factor-alpha / metabolism |
| IF | 3.757 |
| Times Cited | 53 |
| WOS Category | IMMUNOLOGY HEMATOLOGY CELL BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | RAW 264(RCB0535) |