title: Liver fibrosis in bile duct-ligated rats correlates with increased hepatic IL-17 and TGF-β2 expression.
abstract: BACKGROUND AND RATIONALE FOR THE STUDY: IL-17, TGF-β1/2 are cytokines involved in the development of kidney, pulmonary and liver fibrosis. However, their expression kinetics in the pathogenesis of cholestatic liver fibrosis have not yet been fully explored. The aim of the study was to analyze the expression of IL-17, RORγt, NKp46, TGF-β1, and TGF-β2 in the liver of rats with bile duct ligation (BDL).
  
  
  RESULTS
  Hepatic IL-17A gene expression analyzed by qRT-PCR showed a dramatic increase of 350 and 10 fold, at 8 and 30 days post BDL, respectively. TGFβ1 and TGFβ2 gene expression significantly increased throughout the whole fibrotic process. At the protein level in liver homogenates, IL-17, TGF-β1, and RORγt significantly increased at 8 and 30 days after BDL. Interestingly, a significant increase in the protein levels of TGF-β2 and decrease of NKp46 was observed only 30 days after BDL. Unexpectedly, TGF-β2 exhibited stronger signals than TGF-β1 at the gene expression and protein levels. Histological analysis showed bile duct proliferation and collagen deposition.
  
  
  CONCLUSIONS
  Our results suggest that pro-fibrogenic cytokines IL-17, TGF-β1 and, strikingly, TGF-β2 might be important players of liver damage in the pathogenesis of early and advanced experimental cholestatic fibrosis. Th17 cells might represent an important source of IL-17, while NK cell depletion may account for the perpetuation of liver damage in the BDL model.
authors.affiliation: Instituto de Investigación en Enfermedades Crónico-Degenerativas, Departamento de Biología Molecular y Genómica.
authors.forename: Adelaida Sara M
authors.initials: AS
authors.lastname: Zepeda-Morales
authors.affiliation: Laboratorio de Inmunología, Departamento de Fisiología. Centro Universitario de Ciencias de la Salud , Universidad de Guadalajara, Guadalajara, Jal., México.
authors.forename: Susana
authors.initials: S
authors.lastname: Del Toro-Arreola
authors.affiliation: Instituto de Terapéutica Experimental y Clínica, Departamento de Fisiología. Centro Universitario de Ciencias de la Salud , Universidad de Guadalajara, Guadalajara, Jal., México.
authors.forename: Leonel
authors.initials: L
authors.lastname: García-Benavides
authors.affiliation: Instituto de Investigación en Enfermedades Crónico-Degenerativas, Departamento de Biología Molecular y Genómica.
authors.forename: Blanca E
authors.initials: BE
authors.lastname: Bastidas-Ramírez
authors.affiliation: Laboratorio de Inmunología, Departamento de Fisiología. Centro Universitario de Ciencias de la Salud , Universidad de Guadalajara, Guadalajara, Jal., México.
authors.forename: Mary
authors.initials: M
authors.lastname: Fafutis-Morris
authors.affiliation: Laboratorio de Inmunología, Departamento de Fisiología. Centro Universitario de Ciencias de la Salud , Universidad de Guadalajara, Guadalajara, Jal., México.
authors.forename: Ana L
authors.initials: AL
authors.lastname: Pereira-Suárez
authors.affiliation: Instituto de Investigación en Enfermedades Crónico-Degenerativas, Departamento de Biología Molecular y Genómica.
authors.forename: Miriam R
authors.initials: MR
authors.lastname: Bueno-Topete
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D003135:Common Bile Duct / Q000601:surgery*; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000378:metabolism; D008026:Ligation; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000235:genetics / Q000378:metabolism; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D058504:Th17 Cells / Q000378:metabolism; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D053781:Transforming Growth Factor beta2 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C515934:Il17a protein, rat; D020381:Interleukin-17; D055627:Natural Cytotoxicity Triggering Receptor 1; C495388:Ncr1 protein, rat; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539902:Rorc protein, rat; C508962:Tgfb1 protein, rat; C509043:Tgfb2 protein, rat; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D003094:Collagen