Interleukin-6 promotes the migration and cellular senescence and inhibits apoptosis of human intrahepatic biliary epithelial cells

J Cell Biochem. 2018 Feb;119(2):2135-2143. doi: 10.1002/jcb.26375. Epub 2017 Oct 20.

Abstract

Biliary epithelial cells (BEC) are closely related to some immune regulatory bile duct diseases. However, the complexity and polymorphism of the morphology and function of bile duct cells have hindered further investigation. Therefore, the aim of this study is to investigate how interleukin-6 (IL-6) affects the migration, cellular senescence, and apoptosis of human intrahepatic biliary epithelial cells (HIBECs). The HIBECs were stimulated by different concentrations of IL-6 (0, 5, 10, 15, and 20 ng/mL, respectively). Transwell assay was performed in order to measure the migration abilities, positive β-Galactosidase staining for the cellular senescence of HIBECs, MTT assay for changes of proliferation after IL-6 treatment and flow cytometry for cell cycle and apoptosis. The reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting were conducted in order to detect the mRNA and protein expressions of epithelial-mesenchymal transition (EMT) markers in HIBECs. In comparison to the 0 ng/mL group, in the 5, 10, 15, and 20 ng/mL groups, a significant increase in the number of migratory HIBECs, proliferation, along with mRNA and protein expressions of EMT markers was observed. While the mRNA and protein expressions of epithelial markers, the number of β-galactosidase positive staining cells, as well as apoptosis rate of HIBECs dramatic decreased. Further, the aforementioned changes were significantly more evident in the 15 and 20 ng/mL groups in comparison to the 5 and 10 ng/mL groups. IL-6 may stimulate EMT, enhance the migration and proliferation, and inhibit apoptosis of HIBECs, thus delaying cellular senescence.

Keywords: apoptosis; cellular senescence; epithelial-mesenchymal transition; human intrahepatic biliary epithelial cells; interleukin-6; migration.

Publication types

  • Retracted Publication

MeSH terms

  • Apoptosis
  • Bile Ducts, Intrahepatic / cytology*
  • Bile Ducts, Intrahepatic / immunology
  • Biomarkers / analysis
  • Cell Movement
  • Cells, Cultured
  • Cellular Senescence
  • Epithelial Cells / cytology*
  • Epithelial Cells / immunology
  • Epithelial-Mesenchymal Transition*
  • Gene Expression Regulation
  • Humans
  • Interleukin-6 / metabolism*

Substances

  • Biomarkers
  • IL6 protein, human
  • Interleukin-6