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

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

doi:10.1016/j.celrep.2017.01.004

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

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

Tohoku University

Research output: Contribution to journal › Article › peer-review

72 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 language	English
Pages (from-to)	1298-1311
Number of pages	14
Journal	Cell Reports
Volume	18
Issue number	5
DOIs	https://doi.org/10.1016/j.celrep.2017.01.004
Publication status	Published - 2017 Jan 31

Keywords

fibrosis
IL-1α
IL-1β
SiO
SR-BI

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.celrep.2017.01.004

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title = "SR-B1 Is a Silica Receptor that Mediates Canonical Inflammasome Activation",

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.",

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author = "Misato Tsugita and Nobuyuki Morimoto and Manabu Tashiro and Kengo Kinoshita and Masafumi Nakayama",

note = "Funding Information: We thank Drs. Hiromi Yoshida for cell sorting; Masakazu Kawashita for technical advice on inorganic nanoparticles; Toshio Kitamura for pMX vectors; Hisaya Akiba for advice regarding the generation of mAbs; Takashi Sawai, Fumiko Date, and Miki Yoshizawa for histological analysis; and Kazuko Takeda for technical support in human study. This work is supported by Grants-in-Aid for Scientific Research (B) #16H02960 from the Japanese Ministry of Education, Culture, Sports, Science and Technology, a grant from Naito Research Foundation, and a grant from the Sumitomo Science Foundation. This work is also partially supported by the Platform Project for Supporting in Drug Discovery and Life Science Research from Japan Agency for Medical Research and Development (AMED). Publisher Copyright: {\textcopyright} 2017 The Author(s)",

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AU - Nakayama, Masafumi

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N2 - 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.

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

Abstract

Keywords

UN SDGs

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