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-Lewisx (NeuAcα2-3Galβ1-4[Fucα1-3]GlcNAc-R) and 6-sulfo-sialyl-Lewisx (NeuAcα2-3Galβ1-4[Fucα1-3][SO3H-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 α1,3/4-fucosyltransferases [FUT11 (fucosyltransferase 11 gene) and FUT3], α2-6- and α2,3-sialyltransferases [ST3GAL6 (α2,3-sialyltransferase 6 gene) and ST6GAL2 (α2,6-sialyltransferase 2 gene)] and GlcNAc-6-O-sulfotransferases [CHST4 (carbohydrate sulfotransferase 4 gene) and CHST6] mRNA. In parallel, the amounts of sialyl-Lewisx and 6-sulfo-sialyl-Lewisx 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-Lewisx and 6-sulfo-sialyl-Lewisx epitopes on human airway mucins from patients with CF.