Macrophage autophagy protects against XXXX in @entity19 .

@entity15254 @entity4314 @entity82 @entity19 @entity634 @entity635 @entity26 @entity7009 @entity30562 @entity1575 @entity99 @entity18995
Autophagy is a lysosomal degradation pathway of cellular components that displays antiinflammatory properties in macrophages. Macrophages are critically involved in @entity7009 by releasing mediators that promote hepatocyte apoptosis, contribute to inflammatory cell recruitment and activation of hepatic fibrogenic cells. Here, we investigated whether macrophage autophagy may protect against @entity7009 . Experiments were performed in @entity19 with mutations in the autophagy gene @entity15254 in the myeloid lineage ( @entity15254 (fl/fl) @entity30562 -Cre @entity19 , referred to as @entity15254 (-/-)) and their wild-type ( @entity15254 (fl/fl), referred to as WT) littermates. @entity1575 was induced by repeated intraperitoneal injection of @entity4314 . In vitro studies were performed in cultures or co-cultures of peritoneal macrophages with hepatic myofibroblasts. As compared to WT littermates, @entity15254 (-/-) @entity19 exposed to chronic @entity4314 administration displayed higher hepatic levels of @entity634 and @entity635 and enhanced inflammatory cell recruitment associated with exacerbated @entity99 . In addition, @entity15254 (-/-) @entity19 were more susceptible to @entity1575 , as shown by enhanced matrix and fibrogenic cell accumulation. Macrophages from @entity15254 (-/-) @entity19 secreted higher levels of reactive @entity26 species (ROS)-induced @entity634 and @entity635 . Moreover, hepatic myofibroblasts exposed to the conditioned medium of macrophages from @entity15254 (-/-) @entity19 showed increased profibrogenic gene expression; this effect was blunted when neutralizing @entity634 and @entity635 in the conditioned medium of @entity15254 (-/-) macrophages. Finally, administration of recombinant @entity18995 ( @entity18995 ) to @entity4314 -exposed @entity15254 (-/-) @entity19 blunted @entity99 and @entity82 , identifying @entity634 as central mediators in the deleterious effects of macrophage autophagy invalidation. These results uncover macrophage autophagy as a novel antiinflammatory pathway regulating @entity1575 .
