MAFB prevents excess inflammation after ischemic stroke by accelerating clearance of damage signals through MSR1

Takashi Shichita, Minako Ito, Rimpei Morita, Kyoko Komai, Yoshiko Noguchi, Hiroaki Ooboshi, Ryusuke Koshida, Satoru Takahashi, Tatsuhiko Kodama, Akihiko Yoshimura

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Damage-associated molecular patterns (DAMPs) trigger sterile inflammation after tissue injury, but the mechanisms underlying the resolution of inflammation remain unclear. In this study, we demonstrate that common DAMPs, such as high-mobility-group box 1 (HMGB1), peroxiredoxins (PRXs), and S100A8 and S100A9, were internalized through the class A scavenger receptors MSR1 and MARCO in vitro. In ischemic murine brain, DAMP internalization was largely mediated by MSR1. An elevation of MSR1 levels in infiltrating myeloid cells observed 3 d after experimental stroke was dependent on the transcription factor Mafb. Combined deficiency for Msr1 and Marco, or for Mafb alone, in infiltrating myeloid cells caused impaired clearance of DAMPs, more severe inflammation, and exacerbated neuronal injury in a murine model of ischemic stroke. The retinoic acid receptor (RAR) agonist Am80 increased the expression of Mafb, thereby enhancing MSR1 expression. Am80 exhibited therapeutic efficacy when administered, even at 24 h after the onset of experimental stroke. Our findings uncover cellular mechanisms contributing to DAMP clearance in resolution of the sterile inflammation triggered by tissue injury.

Original languageEnglish
JournalNature Medicine
DOIs
Publication statusAccepted/In press - 2017 Apr 10

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MafB Transcription Factor
Class A Scavenger Receptors
Stroke
Tissue
Inflammation
Peroxiredoxins
Retinoic Acid Receptors
Myeloid Cells
Brain
Wounds and Injuries
tamibarotene
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

MAFB prevents excess inflammation after ischemic stroke by accelerating clearance of damage signals through MSR1. / Shichita, Takashi; Ito, Minako; Morita, Rimpei; Komai, Kyoko; Noguchi, Yoshiko; Ooboshi, Hiroaki; Koshida, Ryusuke; Takahashi, Satoru; Kodama, Tatsuhiko; Yoshimura, Akihiko.

In: Nature Medicine, 10.04.2017.

Research output: Contribution to journalArticle

Shichita, Takashi ; Ito, Minako ; Morita, Rimpei ; Komai, Kyoko ; Noguchi, Yoshiko ; Ooboshi, Hiroaki ; Koshida, Ryusuke ; Takahashi, Satoru ; Kodama, Tatsuhiko ; Yoshimura, Akihiko. / MAFB prevents excess inflammation after ischemic stroke by accelerating clearance of damage signals through MSR1. In: Nature Medicine. 2017.
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