The effect of dihydropyrazines on lipopolysaccharide-stimulated human hepatoma hepg2 cells via regulating the TLR4-myd88-mediated NF-κb signaling pathway

Madoka Esaki, Takumi Ishida, Yuu Miyauchi, Shinji Takechi

研究成果: Contribution to journalArticle査読

抄録

Dihydropyrazines (DHPs), including 3-hydro-2,2,5,6-tetramethylpyrazine (DHP-3), are glycation products that are spontaneously generated in vivo and ingested via food. DHPs generate various radicals and reactive oxygen species (ROS), which can induce the expression of several antioxidant genes in HepG2 cells. However, detailed information on DHP-response pathways remains elusive. To address this issue, we investigated the effects of DHP-3 on the nuclear factor-κB (NF-κB) pathway, a ROS-sensi-tive signaling pathway. In lipopolysaccharide-stimulated (LPS-stimulated) HepG2 cells, DHP-3 decreased phosphorylation levels of inhibitor of NF-κB (IκB) and NF-κB p65, and nuclear translocation of NF-κB p65. In addition, DHP-3 reduced the expression of Toll-like receptor 4 (TLR4) and the adaptor protein myeloid differentiation primary response gene 88 (MyD88). Moreover, DHP-3 suppressed the mRNA expression of tumor necrosis factor-alpha (TNFα), and interleukin-1 beta (IL-1β). Taken together, these results suggest that DHP-3 acts as a negative regulator of the TLR4-MyD88-mediated NF-κB signaling pathway.

本文言語英語
ページ(範囲)401-409
ページ数9
ジャーナルJournal of Toxicological Sciences
45
7
DOI
出版ステータス出版済み - 2020

All Science Journal Classification (ASJC) codes

  • Toxicology

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