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

Abstract

There is increasing evidence that inflammation may affect glycosylation and sulfation of various glycoproteins. The present study reports the effect of tumor necrosis factor ␣ (TNF-␣), 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-␣ at a concentration of 20 ng/ml. TNF-␣ was shown to increase ␣1,3-fucosyltransferase activity as well as expression of the two ␣1,3-fucosyltransferase genes expressed in the human airway, FUT3 and FUT4. It had no influence on ␣1,2-fucosyltransferase activity or FUT2 expression. It also increased ␣2,3-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.

Intestinal mucosal alterations in rats with carbon tetrachloride-induced cirrhosis: Changes in glycosylation and luminal bacteria

“…43,44 Studies have shown a role for sialic acid and sugars present on mucosal surfaces as receptors for microorganisms. 9 We find a significant increase in sialic acid, fucose, hexose, and hexosamine in surfactant and BBM in rats only at 3 months after initiation of CCl 4 treatment, which continued to increase until 5 months. These changes could be the result of the oxidative stress, because free radicals can modulate the activity of glycosyltransferase or glycosidases, which might in turn alter glycosylation pattern.…”

“…8 Changes in glycosylation on the surface of intestinal epithelial cells can thus lead to increased bacterial adherence. Reactive oxygen species can modulate glycosylation on the cell surface 9 and also alter the surface viscosity of the mucus, 10 both of which may facilitate bacterial binding. Earlier studies from our laboratory have shown that oxidative stress in the intestinal mucosa after surgical manipulation results in altered glycosylation of the mucosal membranes and bacterial adherence.…”

Helicobacter pylori induces β3GnT5 in human gastric cell lines, modulating expression of the SabA ligand sialyl–Lewis x

“…TNF-α has been shown to stimulate increased expression of several sialyl-, fucosyl-, and sulfotransferases (19). We evaluated the mRNA expression of TNF-α in MKN45 cells infected with Tx30a and 26695 strains and observed that TNF-α was barely detectable in uninfected cells.…”

Article Molecular analysis of three FUT3 gene single nucleotide polymorphisms and their relationship with the lewis erythrocytary phenotype in a human population of japanese-ancestry living in Tomé Açu, a town in the Brazilian Amazon

“…Lewis antigens are particularly important in kidney transplants because rejection is lower in transplants involving Lewis-compatible donors and receptors (Oriol et al, 1978;Williams et al, 1978;Oriol and Danilovics, 1980;Myser et al, 1985;Blajchman et al, 1985;Delmotte et al, 2002), and the molecular test described in this paper may be helpful in avoiding the false negative results sometimes observed whit the serological methods available for typing Lewis antigens.…”