Interleukin-1beta induces sialyl Lewis X on hepatocellular carcinoma HuH-7 cells via enhanced expression of ST3Gal IV and FUT VI gene

FEBS Lett. 2006 Nov 13;580(26):6069-75. doi: 10.1016/j.febslet.2006.09.073. Epub 2006 Oct 12.

Abstract

We previously demonstrated that human hepatocellular carcinoma-derived HuH-7 cells stimulated with interleukin-1beta (IL-1beta) produce alpha(1)-acid glycoprotein (AGP) with increased amounts of sialyl Lewis X (sLeX) antigen, although the mechanism remained obscure. Here, we report our investigation of the mechanism. sLeX expression on HuH-7 cells was induced 2.5 times more after 48 h stimulation with 100 U/mL IL-1 beta compared with control, as indicated by anti-sLeX antibody binding. Furthermore, expression of 2,3-sialylated N-acetyllactosamine increased gradually up to 48 h after IL-1 beta stimulation; this preceded the increase in sLeX expression. Increases in alpha 2,3-sialyltransferase activity also preceded increases in alpha1,3-fucosyltransferase activity. Furthermore, mRNA levels of ST3Gal IV, FUT IV and VI in HuH-7 cells stimulated with IL- 1beta were increased at 2-4 h, while increases in FUT VI mRNA level occurred gradually after 24 h. IL-1 beta-induced sLeX expression on HuH-7 cells was suppressed by transfection of gene-specific small interference RNAs against FUT VI and ST3Gal IV but not against FUT IV and ST3Gal III. These data results that IL-1 beta induces expression of sLeX on HuH-7 cells by enhanced expression of FUT VI and ST3Gal IV gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / biosynthesis
  • Acute-Phase Proteins / genetics
  • Amino Sugars / analysis
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Fucosyltransferases / genetics*
  • Fucosyltransferases / metabolism
  • Gene Expression Regulation / drug effects*
  • Humans
  • Interleukin-1beta / pharmacology*
  • Oligosaccharides / analysis
  • Oligosaccharides / genetics*
  • RNA, Messenger / analysis
  • Sialyl Lewis X Antigen
  • Sialyltransferases / genetics*
  • Up-Regulation / drug effects
  • beta-Galactoside alpha-2,3-Sialyltransferase

Substances

  • Acute-Phase Proteins
  • Amino Sugars
  • Interleukin-1beta
  • Oligosaccharides
  • RNA, Messenger
  • Sialyl Lewis X Antigen
  • lactosamine
  • Fucosyltransferases
  • FUT6 protein, human
  • Sialyltransferases
  • beta-Galactoside alpha-2,3-Sialyltransferase
  • ST3GAL1 protein, human