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

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

Author information

1
Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Sendai 980-8578, Japan.
2
Department of Materials Processing, Graduate School of Engineering, Tohoku University, Sendai 980-8579, Japan.
3
Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai 980-8578, Japan.
4
Graduate School of Information Sciences, Tohoku University, Sendai 980-8579, Japan; Tohoku Medical Megabank Organization, Tohoku University, Sendai 980-8573, Japan.
5
Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Sendai 980-8578, Japan. Electronic address: mnakayama@fris.tohoku.ac.jp.

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

PMID:
28147282
DOI:
10.1016/j.celrep.2017.01.004
[Indexed for MEDLINE]
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