Light induces @entity5704 inflammasome activation in retinal pigment epithelial cells via XXXX -mediated photooxidative damage.

@entity1 @entity6337 @entity5704 @entity1356 @entity467 @entity6973 @entity8923 @entity989 @entity1020 @entity9302
UNASSIGNED: Photooxidative damage and chronic innate immune activation have been implicated in @entity989 ( @entity989 ) dysfunction, a process that underlies blinding diseases such as @entity1020 ( @entity1020 ). To identify a potential molecular link between these mechanisms, we investigated whether @entity6973 -mediated @entity6337 activates the @entity5704 inflammasome in @entity989 cells in vitro. We found that blue light irradiation (dominant wavelength 448  nm, irradiance 0.8  mW/cm(2), duration 6  h) of @entity6973 -loaded primary @entity1 @entity989 cells and @entity1 cells induced photooxidative damage, lysosomal membrane permeabilization (79.5  % of cells vs. 3.8  % in nonirradiated controls), and cytosolic leakage of lysosomal enzymes. This resulted in activation of the inflammasome with activation of @entity9302 and secretion of @entity1356 (14.6 vs. 0.9  pg/ml in nonirradiated controls) and @entity8923 (87.7 vs. 0.2  pg/ml in nonirradiated controls). Interleukin secretion was dependent on the activity of @entity5704 , @entity9302 , and lysosomal proteases @entity467 and L. These results demonstrate that accumulation of @entity6973 -like material in vitro renders @entity989 cells susceptible to phototoxic destabilization of lysosomes, resulting in @entity5704 inflammasome activation and secretion of inflammatory cytokines. This new mechanism of inflammasome activation links photooxidative damage and innate immune activation in @entity989 pathology and may provide novel targets for therapeutic intervention in @entity989 such as @entity1020 . KEY MESSAGE:     Visible light irradiation of @entity6973 -loaded @entity989 cells activates inflammasome.     Inflammasome activation results from lysosomal permeabilization and enzyme leakage.     Inflammasome activation induces secretion of inflammatory cytokines by @entity989 cells.     Photooxidative damage by visible light as new mechanism of inflammasome activation.     Novel link between hallmark pathogenetic features of @entity989 .
