TLR4 signaling inhibitory pathway induced by green tea polyphenol epigallocatechin-3-gallate through 67-kDa laminin receptor

Eui Hong Byun, Yoshinori Fujimura, Koji Yamada, Hirofumi Tachibana

Research output: Contribution to journalArticlepeer-review

134 Citations (Scopus)

Abstract

Epigallocatechin-3-gallate (EGCG), a major active polyphenol of green tea, has been shown to downregulate inflammatory responses in macrophages; however, the underlying mechanism has not been understood. Recently, we identified the 67-kDa laminin receptor (67LR) as a cell-surface EGCG receptor that mediates the anticancer action of EGCG at physiologically relevant concentrations (0.1-1 μM). In this study, we show the molecular basis for the downregulation of TLR4 signal transduction by EGCG at 1 μM in macrophages. Anti-67LR Ab treatment or RNA interference-mediated silencing of 67LR resulted in abrogation of the inhibitory action of EGCG on LPS-induced activation of downstream signaling pathways and target gene expressions. Additionally, we found that EGCG reduced the TLR4 expression through 67LR. Interestingly, EGCG induced a rapid upregulation of Toll-interacting protein (Tollip), a negative regulator of TLR signaling, and this EGCG action was prevented by 67LR silencing or anti-67LR Ab treatment. RNA interference-mediated silencing of Tollip impaired the TLR4 signaling inhibitory activity of EGCG. Taken together, these findings demonstrate that 67LR plays a critical role in mediating anti-inflammatory action of a physiologically relevant EGCG, and Tollip expression could be modulated through 67LR. These results provide a new insight into the understanding of negative regulatory mechanisms for the TLR4 signaling pathway and consequent inflammatory responses that are implicated in the development and progression of many chronic diseases.

Original languageEnglish
Pages (from-to)33-45
Number of pages13
JournalJournal of Immunology
Volume185
Issue number1
DOIs
Publication statusPublished - Jul 1 2010

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'TLR4 signaling inhibitory pathway induced by green tea polyphenol epigallocatechin-3-gallate through 67-kDa laminin receptor'. Together they form a unique fingerprint.

Cite this