Interleukin-1beta induces sialyl Lewis X on hepatocellular carcinoma HuH-7 cells via enhanced expression of ST3Gal IV and FUT VI gene.
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.
Higai
Koji
K
Department of Clinical Chemistry, School of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi, Chiba 274-8510, Japan. koji@phar.toho-u.ac.jp
Miyazaki
Noriko
N
Azuma
Yutaro
Y
Matsumoto
Kojiro
K
D000209:Acute-Phase Proteins / Q000096:biosynthesis / Q000235:genetics; D000606:Amino Sugars / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D005647:Fucosyltransferases / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D009844:Oligosaccharides / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D000080506:Sialyl Lewis X Antigen; D012799:Sialyltransferases / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
D000209:Acute-Phase Proteins; D000606:Amino Sugars; D053583:Interleukin-1beta; D009844:Oligosaccharides; D012333:RNA, Messenger; D000080506:Sialyl Lewis X Antigen; C032233:lactosamine; D005647:Fucosyltransferases; C515956:FUT6 protein, human; D012799:Sialyltransferases; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase; C000722087:ST3GAL1 protein, human