SR-B1 Is a Silica Receptor that Mediates Canonical Inflammasome Activation.
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.
Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Sendai 980-8578, Japan.
Misato
M
Tsugita
Department of Materials Processing, Graduate School of Engineering, Tohoku University, Sendai 980-8579, Japan.
Nobuyuki
N
Morimoto
Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai 980-8578, Japan.
Manabu
M
Tashiro
Graduate School of Information Sciences, Tohoku University, Sendai 980-8579, Japan; Tohoku Medical Megabank Organization, Tohoku University, Sendai 980-8573, Japan.
Kengo
K
Kinoshita
Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Sendai 980-8578, Japan. Electronic address: mnakayama@fris.tohoku.ac.jp.
Masafumi
M
Nakayama
D000818:Animals; D020170:Caspase 1 / Q000378:metabolism; D002460:Cell Line; D057809:HEK293 Cells; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism; D041681:NIH 3T3 Cells; D011014:Pneumonia / Q000378:metabolism; D051116:Receptors, Scavenger / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000378:metabolism*; D012822:Silicon Dioxide / Q000378:metabolism*
D058847:Inflammasomes; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D012822:Silicon Dioxide; D020170:Caspase 1
IL-1α; IL-1β; SR-BI; SiO(2); fibrosis