title: The inflammasome in liver injury and non-alcoholic fatty liver disease.
abstract: The liver possesses a strong inflammatory response, as seen experimentally and clinically with liver inflammation due to toxic and metabolic stress, sepsis and ischemia. Initiation of this inflammatory response requires the interaction of two types of extracellular signals which collectively upregulate and activate a cytosolic molecular complex termed the inflammasome. Signal 1 is via activation of pattern recognition receptors, and signal 2 is delivered by diverse stimuli including particulates and adenosine triphosphate. The common end result of inflammasome activation is the activation of the protease caspase-1 with release of active interleukin-1β. The inflammasome is important in a wide range of conditions including alcoholic and non-alcoholic steatohepatitis. Kupffer cells are known to be important, but the consequences of inflammasome activation in other hepatic immune cells have not been well characterized. The inflammasome pathway is also known to be required for a full fibrotic response, as demonstrated by reduced lung, skin and liver fibrosis in inflammasome-deficient mice. Identification of the inflammasome machinery has opened up novel therapeutic avenues by the use of antagonists for Toll-like receptors as well as the adenosine triphosphate receptor P2X7, and the interleukin-1 receptor. There is now great interest in how inflammasome pathways are regulated. The initial challenge is to understand how an acute inflammatory response is sustained. This is a significant issue as the known stimuli result in an acute response that is self-limited to under 24 h. This suggests that there are significant regulators which allow sustained inflammasome activation in conditions such as non-alcoholic steatohepatitis and alcoholic hepatitis.
authors.affiliation: Section of Digestive Diseases, Yale University, New Haven, Conn., and Section of Digestive Diseases, Department of Veterans Affairs Connecticut Healthcare, West Haven, Conn., USA.
authors.forename: Wajahat Zafar
authors.initials: WZ
authors.lastname: Mehal
mesh_terms: D000818:Animals; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation / Q000473:pathology; D008099:Liver / Q000293:injuries* / Q000473:pathology*; D008103:Liver Cirrhosis / Q000473:pathology; D065626:Non-alcoholic Fatty Liver Disease / Q000473:pathology*; D051192:Receptors, Pattern Recognition / Q000378:metabolism
chemical_list: D058847:Inflammasomes; D051192:Receptors, Pattern Recognition