Glycyrrhizin and isoliquiritigenin suppress the LPS sensor Toll-like receptor 4/MD-2 complex signaling in a different manner
In: Journal of Leukocyte Biology, Jg. 91 (2012-06-01), S. 967-976
Online
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Zugriff:
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.
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Glycyrrhizin and isoliquiritigenin suppress the LPS sensor Toll-like receptor 4/MD-2 complex signaling in a different manner
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Autor/in / Beteiligte Person: | Hayashi, Hiroaki ; Saitoh, Shin-ichiro ; Muraguchi, Atsushi ; Fujii, Isao ; Miyake, Kensuke ; Honda, Hiroe ; Matsunaga, Takayuki ; Nagai, Yoshinori ; Takatsu, Kiyoshi ; Akashi-Takamura, Sachiko |
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Zeitschrift: | Journal of Leukocyte Biology, Jg. 91 (2012-06-01), S. 967-976 |
Veröffentlichung: | Oxford University Press (OUP), 2012 |
Medientyp: | unknown |
ISSN: | 1938-3673 (print) ; 0741-5400 (print) |
DOI: | 10.1189/jlb.0112038 |
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