Role of scavenger receptors as damage-associated molecular pattern receptors in Toll-like receptor activation

Kyoko Komai, Takashi Shichita, Minako Ito, Mitsuhiro Kanamori, Shunsuke Chikuma, Akihiko Yoshimura

研究成果: Contribution to journalArticle査読

17 被引用数 (Scopus)

抄録

Damage-associated molecular patterns (DAMPs) have been implicated in sterile inflammation in various tissue injuries. High-mobility group box 1 (HMGB1) is a representative DAMP, and has been shown to transmit signals through receptors for advanced glycation end products (RAGEs) and TLRs, including TLR2 and TLR4. HMGB1 does not, however, bind to TLRs with high affinity; therefore, the mechanism of HMGB1-mediated TLR activation remains unclear. In this study, we found that fluorescently labeled HMGB1 was efficiently internalized into macrophages through class A scavenger receptors. Although both M1- and M2-type macrophages internalized HMGB1, only M1-type macrophages secreted cytokines in response to HMGB1. The pan-class A scavenger receptor competitive inhibitor, maleylated bovine serum albumin (M-BSA), inhibited HMGB1 internalization and reduced cytokine production from macrophages in response to HMGB1 but not to LPS. The C-terminal acidic domain of HMGB1 is responsible for scavenger receptor-mediated internalization and cytokine production. HMGB1 and TLR4 co-localized in macrophages, and this interaction was disrupted by M-BSA, suggesting that class A scavenger receptors function as co-receptors of HMGB1 for TLR activation. M-BSA ameliorated LPS-induced sepsis and dextran sulfate sodium (DSS)-induced colitis models in which HMGB1 has been shown to play progressive roles. These data suggest that scavenger receptors function as co-receptors along with TLRs for HMGB1 in M1-type inflammatory macrophages.

本文言語英語
ページ(範囲)59-70
ページ数12
ジャーナルInternational immunology
29
2
DOI
出版ステータス出版済み - 2 1 2017
外部発表はい

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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