title: Activated farnesoid X receptor attenuates apoptosis and liver injury in autoimmune hepatitis.
abstract: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease associated with interface hepatitis, the presence of autoantibodies, regulatory T‑cell dysfunction and raised plasma liver enzyme levels. The present study assessed the hepatoprotective and antiapoptotic role of farnesoid X receptor (FXR) in AIH. a mouse model of AIH was induced by treatment with concanavalin A (ConA). The FXR agonist, chenodeoxycholic acid (CDCA), was administered to mice exhibiting ConA‑induced liver injury and a normal control. Blood samples were obtained to detect the levels of aminotransferases and inflammatory cytokines. Liver specimens were collected, and hematoxylin‑eosin staining was used for histopathological examination and detection. Apoptosis was evaluated using the terminal deoxynucleotidyl-transferase‑mediated dUTP nick end labeling (TUNEL) method. The expression levels of apoptosis‑associated genes and proteins were determined by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. The results demonstrated that FXR was downregulated at the mRNA and protein level in the liver specimens of mice induced with ConA‑induced hepatitis. Increased levels of aminotransferases and inflammatory cytokines, including interferon‑γ, tumor necrosis factor‑α, interleukin (IL)‑4 and IL‑2, were detected in ConA‑treated mice. The mice pretreated with the FXR agonist, CDCA, were more resistant to ConA hepatitis, as indicated by reduced levels of alanine transaminase/aspartate aminotransferase and aminotransferases. The activation of FXR ameliorated hepatocyte apoptosis, as demonstrated by TUNEL analysis and downregulation of the Fas/Fas ligand, tumor necrosis factor‑related apoptosis‑inducing ligand and caspase‑3. Taken together, FXR activation ameliorated liver injury and suppressed inflammatory cytokines in ConA‑induced hepatitis. FXR, therefore, exerts a protective role against ConA-induced apoptosis.
authors.affiliation: Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Lian
authors.affiliation: Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Youjun
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Zhongshan School of Medicine, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Xiwen
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Hanshi
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Liuqin
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Xiuyan
authors.initials: X
authors.lastname: Yang
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D001219:Aspartate Aminotransferases / Q000097:blood; D053148:Caspase 3 / Q000235:genetics / Q000276:immunology; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D003208:Concanavalin A / Q000008:administration & dosage; D004195:Disease Models, Animal; D053222:Fas Ligand Protein / Q000235:genetics / Q000276:immunology; D005260:Female; D005765:Gastrointestinal Agents / Q000494:pharmacology; D005786:Gene Expression Regulation; D019693:Hepatitis, Autoimmune / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D022781:Hepatocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D008099:Liver / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D019014:fas Receptor / Q000235:genetics / Q000276:immunology; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D053148:Caspase 3; D002635:Chenodeoxycholic Acid; D003208:Concanavalin A; D053222:Fas Ligand Protein; D005765:Gastrointestinal Agents; D007371:Interferon-gamma; D007376:Interleukin-2; D015847:Interleukin-4; D018160:Receptors, Cytoplasmic and Nuclear; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D000099150:Receptor, Farnesoid X-Activated; C491899:Fas protein, mouse