Tumor Necrosis Factor α Increases the Expression of Glycosyltransferases and Sulfotransferases Responsible for the Biosynthesis of Sialylated and/or Sulfated Lewis x Epitopes in the Human Bronchial Mucosa

• Published in: The Journal of biological chemistry 2002-01, Vol.277 (1), p.424
• Main Authors: Philippe Delmotte, Sophie Degroote, Jean-Jacques Lafitte, Geneviève Lamblin, Jean-Marc Perini, Philippe Roussel
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M109958200

There is increasing evidence that inflammation may affect glycosylation and sulfation of various glycoproteins. The present study reports the effect of tumor necrosis factor α (TNF-α), 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-α at a concentration of 20 ng/ml. TNF-α was shown to increase α1,3-fucosyltransferase activity as well as expression of the two α1,3-fucosyltransferase genes expressed in the human airway, FUT3 and FUT4. It had no influence on α1,2-fucosyltransferase activity or FUT2 expression. It also increased α2,3-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.