SR-B1 Is a Silica Receptor that Mediates Canonical Inflammasome Activation

Misato Tsugita, Nobuyuki Morimoto, Manabu Tashiro, Kengo Kinoshita, Masafumi Nakayama

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The inhalation of silica dust is associated with fibrosis and lung cancer, which are triggered by macrophage inflammatory responses; however, how macrophages recognize silica remains largely unknown. Here, we identify by functional expression cloning the class B scavenger receptor SR-B1 as a silica receptor. Through an extracellular α-helix, both mouse and human SR-B1 specifically recognized amorphous and crystalline silica, but not titanium dioxide nanoparticles, latex nanoparticles, or monosodium urate crystals, although all particles exhibited negative surface potentials. Genetic deletion of SR-B1 and masking of SR-B1 by monoclonal antibodies showed that SR-B1-mediated recognition of silica is associated with caspase-1-mediated inflammatory responses in mouse macrophages and human peripheral blood monocytes. Furthermore, SR-B1 was involved in silica-induced pulmonary inflammation in mice. These results indicate that SR-B1 is a silica receptor associated with canonical inflammasome activation.

Original languageEnglish
Pages (from-to)1298-1311
Number of pages14
JournalCell Reports
Volume18
Issue number5
DOIs
Publication statusPublished - 2017 Jan 31

Keywords

  • IL-1α
  • IL-1β
  • SR-BI
  • SiO
  • fibrosis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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