title: IL-6 and IL-8 increase the expression of glycosyltransferases and sulfotransferases involved in the biosynthesis of sialylated and/or sulfated Lewisx epitopes in the human bronchial mucosa.
abstract: Bronchial mucins from patients suffering from CF (cystic fibrosis) exhibit glycosylation alterations, especially increased amounts of the sialyl-Lewis(x) (NeuAcalpha2-3Galbeta1-4[Fucalpha1-3]GlcNAc-R) and 6-sulfo-sialyl-Lewis(x) (NeuAcalpha2-3Galbeta1-4[Fucalpha1-3][SO(3)H-6]GlcNAc-R) terminal structures. These epitopes are preferential receptors for Pseudomonas aeruginosa, the bacteria responsible for the chronicity of airway infection and involved in the morbidity and early death of CF patients. However, these glycosylation changes cannot be directly linked to defects in CFTR (CF 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 incubation of macroscopically healthy fragments of human bronchial mucosa with IL-6 (interleukin-6) or IL-8 results in a significant increase in the expression of alpha1,3/4-fucosyltransferases [FUT11 (fucosyltransferase 11 gene) and FUT3], alpha2-6- and alpha2,3-sialyltransferases [ST3GAL6 (alpha2,3-sialyltransferase 6 gene) and ST6GAL2 (alpha2,6-sialyltransferase 2 gene)] and GlcNAc-6-O-sulfotransferases [CHST4 (carbohydrate sulfotransferase 4 gene) and CHST6] mRNA. In parallel, the amounts of sialyl-Lewis(x) and 6-sulfo-sialyl-Lewis(x) epitopes at the periphery of high-molecular-mass proteins, including MUC4, were also increased. In conclusion, our results indicate that IL-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 CF.
authors.affiliation: Unité de Glycobiologie Structurale et Fonctionnelle, UMR CNRS No. 8576, Bâtiment C9, Université des Sciences et Technologies de Lille, F-59655 Villeneuve d'Ascq, Lille, France. Sophie.Groux-Degroote@univ-lille1.fr
authors.forename: Sophie
authors.initials: S
authors.lastname: Groux-Degroote
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Krzewinski-Recchi
authors.forename: Aurélie
authors.initials: A
authors.lastname: Cazet
authors.forename: Audrey
authors.initials: A
authors.lastname: Vincent
authors.forename: Sylvain
authors.initials: S
authors.lastname: Lehoux
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Lafitte
authors.forename: Isabelle
authors.initials: I
authors.lastname: Van Seuningen
authors.forename: Philippe
authors.initials: P
authors.lastname: Delannoy
mesh_terms: D001980:Bronchi / Q000201:enzymology*; D003550:Cystic Fibrosis / Q000276:immunology; D000939:Epitopes / Q000096:biosynthesis*; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism*; D016695:Glycosyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D016209:Interleukin-8 / Q000502:physiology*; D016256:Lewis X Antigen / Q000096:biosynthesis* / Q000378:metabolism; D009092:Mucous Membrane / Q000201:enzymology; D016133:Polymerase Chain Reaction; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000939:Epitopes; D015850:Interleukin-6; D016209:Interleukin-8; D016256:Lewis X Antigen; D016695:Glycosyltransferases; C000588690:FUT11 protein, human; D005647:Fucosyltransferases; D015238:Sulfotransferases