Regulation of sialyl-Lewis x epitope expression by TNF-alpha and EGF in an airway carcinoma cell line.
Sialyl-Lewis x epitopes and MUC5AC protein are known to be overexpressed in mucins secreted by patients suffering from various respiratory diseases. To investigate the mechanisms by which airway inflammatory agents mediate the expression of sialyl-Lewis x epitopes and MUC5AC mucin, we examined the effects of tumor necrosis factor (TNF)-alpha and epidermal growth factor (EGF) in the human lung carcinoma cell line, NCI-H292. Basal expression levels of hST3GalIV, FUT3 and C2/4GnT mRNA, involved in the biosynthesis of sialyl-Lewis x, were higher than those of other glycosyltransferases in NCI-H292 cells. TNF-alpha induced expression of hST3GalIV, FUT3, C2/4GnT and MUC5AC mRNAs in NCI-H292 cells. When cells were pretreated with U73122, a phosphatidylinositol-phospholipase C (PI-PLC) inhibitor, the expression of these glycosyltransferase mRNAs was suppressed. Treating cells with EGF induced the down-regulation of these glycosyltransferase mRNAs and sialyl-Lewis x epitopes, while inducing an increase in expression of MUC5AC mRNA. These EGF-mediated effects on the glycosyltransferase and MUC5AC mRNAs were blocked when cells were first exposed to AG1478, an EGF receptor tyrosine kinase inhibitor. These findings suggest that the expression of sialyl-Lewis x epitopes, which is regulated separately from the expression of MUC5AC protein, may be controlled through pathways such as the EGF receptor tyrosine kinase and PI-PLC signaling cascades in NCI-H292 cells.
Ishibashi
Yuji
Y
Bionic Materials Technology Group, Biomaterials Center, National Institute for Materials Science, Ibaraki, Japan.
Inouye
Yoshio
Y
Okano
Teruo
T
Taniguchi
Akiyoshi
A
D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D000939:Epitopes; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D008175:Lung Neoplasms; D055271:Mucin 5AC; D009077:Mucins / Q000096:biosynthesis / Q000235:genetics; D009844:Oligosaccharides / Q000096:biosynthesis* / Q000235:genetics; D043265:Phosphatidylinositol Diacylglycerol-Lyase / Q000037:antagonists & inhibitors / Q000502:physiology; D054801:Phosphoinositide Phospholipase C; D012333:RNA, Messenger / Q000096:biosynthesis; D000080506:Sialyl Lewis X Antigen; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
D000939:Epitopes; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; D009844:Oligosaccharides; D012333:RNA, Messenger; D000080506:Sialyl Lewis X Antigen; D014409:Tumor Necrosis Factor-alpha; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D054801:Phosphoinositide Phospholipase C; D043265:Phosphatidylinositol Diacylglycerol-Lyase