Adelaida Sara M. Zepeda-Morales, Susana Del Toro-Arreola, Leonel García-Benavides, Blanca E. Bastidas-Ramírez, Mary Fafutis-Morris, Ana L. Pereira-Suárez, Miriam R. Bueno-Topete
Background and rationale for the study. IL-17, TGF-B1/2 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, ROR?t, NKp46, TGF-B1, and TGF-B2 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. TGFB1 and TGFB2 gene expression significantly increased throughout the whole fibrotic process. At the protein level in liver homogenates, IL-17, TGF-B1, and ROR?t significantly increased at 8 and 30 days after BDL. Interestingly, a significant increase in the protein levels of TGF-B2 and decrease of NKp46 was observed only 30 days after BDL. Unexpectedly, TGF-B2 exhibited stronger signals than TGF-B1 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-B1 and, strikingly, TGF-B2 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.
Key words. ROR ?, TGF-?, NK cells bile duct ligation