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

Publication date: 31 January 2017
Source:Cell Reports, Volume 18, Issue 5
Author(s): Misato Tsugita, Nobuyuki Morimoto, Manabu Tashiro, Kengo Kinoshita, Masafumi Nakayama
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.

Graphical abstract

Teaser

Recognition of silica by macrophages causes inflammation associated with fibrosis and cancer, but how macrophages recognize silica remains unclear. Tsugita et al. now identify SR-B1 as a silica receptor that mediates canonical inflammasome activation and subsequent lung inflammation.


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