Tumor necrosis factor alpha increases the expression of glycosyltransferases and sulfotransferases responsible for the biosynthesis of sialylated and/or sulfated Lewis x epitopes in the human bronchial mucosa.
There is increasing evidence that inflammation may affect glycosylation and sulfation of various glycoproteins. The present study reports the effect of tumor necrosis factor alpha (TNF-alpha), a proinflammatory cytokine, on the glycosyl- and sulfotransferases of the human bronchial mucosa responsible for the biosynthesis of Lewis x epitope and of its sialylated and/or sulfated derivatives, which are expressed in human bronchial mucins. Fragments of macroscopically normal human bronchial mucosa were exposed to TNF-alpha at a concentration of 20 ng/ml. TNF-alpha was shown to increase alpha1,3-fucosyltransferase activity as well as expression of the two alpha1,3-fucosyltransferase genes expressed in the human airway, FUT3 and FUT4. It had no influence on alpha1,2-fucosyltransferase activity or FUT2 expression. It also increased alpha2,3-sialyltransferase activity and the expression of ST3Gal-III and, more importantly, ST3Gal-IV and both N-acetylglucosamine 6-O-sulfotransferase and galactose 3-O-sulfotransferase. These results are consistent with the observation of oversialylation and increased expression sialyl-Lewis x epitopes on human airway mucins secreted by patients with severe lung infection such as those with cystic fibrosis, whose airways are colonized by Pseudomonas aeruginosa. However, other cytokines may also be involved in this process.
Delmotte
Philippe
P
INSERM U 377 and Université de Lille 2, 59045 Lille Cedex, France.
Degroote
Sophie
S
Lafitte
Jean-Jacques
JJ
Lamblin
Geneviève
G
Perini
Jean-Marc
JM
Roussel
Philippe
P
D001980:Bronchi / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005647:Fucosyltransferases / Q000096:biosynthesis; D006031:Glycosylation; D016695:Glycosyltransferases / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D016256:Lewis X Antigen / Q000096:biosynthesis*; D009844:Oligosaccharides / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis; D000080506:Sialyl Lewis X Antigen; D012799:Sialyltransferases / Q000096:biosynthesis; D015238:Sulfotransferases / Q000096:biosynthesis* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016256:Lewis X Antigen; D009844:Oligosaccharides; D012333:RNA, Messenger; D000080506:Sialyl Lewis X Antigen; D014409:Tumor Necrosis Factor-alpha; D016695:Glycosyltransferases; D005647:Fucosyltransferases; D012799:Sialyltransferases; D015238:Sulfotransferases