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

Abstract

We previously demonstrated that human hepatocellular carcinoma-derived HuH-7 cells stimulated with interleukin1b (IL-1b) produce a 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-1b 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-1b stimulation; this preceded the increase in sLeX expression. Increases in a2,3-sialyltransferase activity also preceded increases in a1,3-fucosyltransferase activity. Furthermore, mRNA levels of ST3Gal IV, FUT IV and VI in HuH-7 cells stimulated with IL-1b were increased at 2-4 h, while increases in FUT VI mRNA level occurred gradually after 24 h. IL-1b-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-1b induces expression of sLeX on HuH-7 cells by enhanced expression of FUT VI and ST3Gal IV gene.

Characterization of Membrane-shed Microvesicles from Cytokine-stimulated β-Cells Using Proteomics Strategies

“…Several sialyltransferases and glycosyltransferases have been shown to change in abundance as a consequence of cytokine treatment. For example, ␣2,3-sialyltransferases are increasing upon TNF␣ treatment (81), and the sialyltransferase ST3Gal IV is increasing upon IL-1␤ stimulation (28). This change in sialyltranferase will have a direct effect on the level of sialylation of glycopeptides, and this could be in agreement with our observations.…”

O-Glycan inhibitors generate aryl-glycans, induce apoptosis and lead to growth inhibition in colorectal cancer cell lines

“…The low level of Oglycan sialylation and the absence of sialyl-Le a in aryl-glycans (Table IV) are supported by the deficiency of ST3GAL1 and ST3GAL3 expression. The detection of sialyl-Lewis X (sialylLe x ) in aryl-glycans (17 and 25) is consistent with the action of ST3GAL4 (Higai et al 2006), together with FUT3 and B3GALT5. The very low expression of α2-6-linked sialic acid to GalNAc in aryl-glycans is notable as this structure is a major feature of the glycans found in mucins from PC/AA/C1/SB10C cells.…”

Alteration of the Serum N-glycome of Mice Locally Exposed to High Doses of Ionizing Radiation

“…Moreover, the mRNA levels of sialyltransferases (ST3GAL4, ST6GAL1, and ST6GALNAC6) were upregulated in the liver at day 14 post-irradiation. Furthermore, ST6GAL1, which is highly expressed in the liver (47), has been shown to be up-regulated by IL-6 (48) and TNF␣ (49,50), and the expression of ST3GAL4 was increased by IL-1␤ (51). An induction of IL-1␤, IL-6, and TNF␣ following irradiation of the skin might therefore explain the observed increase in serum sialylated glycans after radiation exposure.…”