title: Absent in melanoma 2 triggers a heightened inflammasome response in ascitic fluid macrophages of patients with cirrhosis.
abstract: OBJECTIVE
  Inflammation is a common event in the pathogenesis of liver cirrhosis. The inflammasome pathway has acquired significant relevance in the pathogenesis of inflammation, but its role in the inflammatory response in patients with decompensated cirrhosis remains unexplored.
  
  
  METHODS
  We performed a prospective study in which 44 patients with decompensated cirrhosis and 12 healthy volunteers were included. We isolated macrophages from blood and ascitic fluid and assessed the expression and activation of the inflammasome, its response to priming by bacterial products, and its association with the degree of liver disease.
  
  
  RESULTS
  Macrophages from sterile ascitic fluids showed constitutive activation of caspase-1 and a marked increase in the expression of IL-1β, IL-18, and absent in melanoma 2 (AIM2) when compared to blood macrophages. Pre-stimulation of blood-derived macrophages from cirrhotic patients with bacterial DNA increased the expression of AIM2 and induced a higher AIM2-mediated inflammasome response than priming with other bacterial products such as lipopolysaccharide. By contrast, activation of the AIM2 inflammasome did not require a priming signal in ascitic fluid-derived macrophages, demonstrating the preactivated state of the inflammasome in these cells. Last, higher IL-1β and IL-18 production by ascitic fluid macrophages correlated with a more advanced Child-Pugh score.
  
  
  CONCLUSIONS
  The inflammasome is highly activated in the ascitic fluid of cirrhotic patients, which may explain the exacerbated inflammatory response observed in these patients under non-infected conditions. Clinically, activation of the inflammasome is associated with a higher degree of liver disease.
authors.affiliation: Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Lozano-Ruiz
authors.affiliation: Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Bachiller
authors.affiliation: Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Irma
authors.initials: I
authors.lastname: García-Martínez
authors.affiliation: Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Pharmacology Unit, Hospital General Universitario de Alicante, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Zapater
authors.affiliation: Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Gómez-Hurtado
authors.affiliation: Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Moratalla
authors.affiliation: Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Giménez
authors.affiliation: Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Bellot
authors.affiliation: Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Department of Clinical Medicine, University Miguel Hernández, Elche, Alicante, Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: Francés
authors.affiliation: Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Department of Clinical Medicine, University Miguel Hernández, Elche, Alicante, Spain; Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates.
authors.forename: José
authors.initials: J
authors.lastname: Such
authors.affiliation: Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: gonzalez_josnav@gva.es.
authors.forename: José M
authors.initials: JM
authors.lastname: González-Navajas
mesh_terms: D000328:Adult; D000368:Aged; D001202:Ascitic Fluid / Q000166:cytology*; D015153:Blotting, Western; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C410167:AIM2 protein, human; D016207:Cytokines; D004268:DNA-Binding Proteins; D058847:Inflammasomes; D004247:DNA
keywords: Absent in melanoma 2; Ascitic fluid; Inflammasome