Effects of carbocisteine on sialyl-Lewis x expression in an airway carcinoma cell line stimulated with tumor necrosis factor-alpha.
Carbocisteine is a mucoregulatory drug normalizing sialic acid and fucose contents in mucins through the regulation of glycosyltransferase activities. Tumor necrosis factor (TNF)-alpha-induced overexpression of sialyl-Lewis x epitopes, containing sialic acid and fucose, in mucins were previously reported to be regulated by glycosyltransferase mRNAs expression through phosphatidyl inositol-specific phospholipase C (PI-PLC) signaling pathways [Ishibashi, Y., Inouye, Y., Okano, T., Taniguchi, A., 2005. Regulation of sialyl-Lewis x epitope expression by TNF-alpha and EGF in an airway carcinoma cell line. Glycoconj. J. 22, 53-62]. To investigate the mechanism behind the mucoregulatory action of carbocisteine, the present study evaluated the effects of carbocisteine on TNF-alpha-induced overexpression of sialyl-Lewis x epitopes in NCI-H292 cells. 100 mug/ml of carbocisteine was able to inhibit the TNF-alpha-induced expression of hST3GallV mRNA, FUT3 mRNA, C2/4GnT mRNA and sialyl-Lewis x epitopes as well as the TNF-alpha-induced activity of PI-PLC in NCI-H292 cells. These findings suggest that carbocisteine may normalize the sialyl-Lewis x epitopes expression in mucins through the inhibition of cellular PI-PLC activity in vivo.
Ishibashi
Yuji
Y
Bionic Materials Technology Group, Biomaterials Center, National Institute for Materials Science, 305-0044 Ibaraki, Japan. yuuji.ishibashi@mb.kyorin-pharm.co.jp
Imai
Shigeru
S
Inouye
Yoshio
Y
Okano
Teruo
T
Taniguchi
Akiyoshi
A
D002233:Carbocysteine / Q000494:pharmacology*; D002277:Carcinoma; D045744:Cell Line, Tumor; D000939:Epitopes; D005100:Expectorants / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D016695:Glycosyltransferases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms; D009844:Oligosaccharides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D043265:Phosphatidylinositol Diacylglycerol-Lyase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054801:Phosphoinositide Phospholipase C; D012333:RNA, Messenger / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen; D014409:Tumor Necrosis Factor-alpha
D000939:Epitopes; D005100:Expectorants; D009844:Oligosaccharides; D012333:RNA, Messenger; D000080506:Sialyl Lewis X Antigen; D014409:Tumor Necrosis Factor-alpha; D002233:Carbocysteine; D016695:Glycosyltransferases; D054801:Phosphoinositide Phospholipase C; D043265:Phosphatidylinositol Diacylglycerol-Lyase