IL-6 and IL-8 increase the expression of glycosyltransferases and sulfotransferases involved in the biosynthesis of sialylated and/or sulfated Lewis x} epitopes in the human bronchial mucosa
Résumé
Bronchial mucins from patients suffering from cystic fibrosis exhibit glycosylation alterations, especially increased amounts of the sialyl-Lewis x} (NeuAcα2-3Galβ1-4[Fucα1-3]GlcNAc-R) and 6-sulfo-sialyl-Lewis x} (NeuAcα2-3Galβ1-4[Fucα1-3][SO3H-6]GlcNAc-R) terminal structures. These epitopes are preferential receptors for P. aeruginosa, the bacteria responsible for the chronicity of airway infection and involved in the morbidity and early death of cystic fibrosis patients. However, these glycosylation changes cannot be directly linked to defects in Cystic Fibrosis Transmembrane conductance Regulator gene expression since cells that secrete airway mucins express no or very low amounts of the protein. Several studies have shown that inflammation may affect glycosylation and sulfation of various glycoproteins, including mucins. In the present study, we show that incubations of macroscopically healthy fragments of human bronchial mucosa with interleukin 6 or 8 result in a significant increase of the expression of α1,3/4-fucosyltransferases (FUT11 and FUT3), α2,6- and α2,3-sialyltransferases (ST3GAL6 and ST6GAL2), and GlcNAc-6-O-sulfotransferases (CHST4 and CHST6) mRNA. In parallel, the amounts of sialyl-Lewis x} and 6-sulfo-sialyl-Lewis x} epitopes at the periphery of high molecular weight proteins, including MUC4, was also increased. In conclusion, our results indicate that interleukin 6 and 8 may contribute to the increased levels of sialyl-Lewis x} and 6-sulfo-sialyl-Lewis x} epitopes on human airway mucins from patients with cystic fibrosis.
Domaines
Biochimie, Biologie Moléculaire
Origine : Fichiers produits par l'(les) auteur(s)
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