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

Cell Rep. 2017 Jan 31;18(5):1298-1311. doi: 10.1016/j.celrep.2017.01.004.

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.

Keywords: IL-1α; IL-1β; SR-BI; SiO(2); fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspase 1 / metabolism
  • Cell Line
  • HEK293 Cells
  • Humans
  • Inflammasomes / metabolism*
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Monocytes / metabolism
  • NIH 3T3 Cells
  • Pneumonia / metabolism
  • Receptors, Scavenger / metabolism
  • Scavenger Receptors, Class B / metabolism*
  • Silicon Dioxide / metabolism*

Substances

  • Inflammasomes
  • Receptors, Scavenger
  • Scarb1 protein, mouse
  • Scavenger Receptors, Class B
  • Silicon Dioxide
  • Caspase 1