TNF induces the expression of the sialyltransferase ST3Gal IV in human bronchial mucosa via MSK1/2 protein kinases and increases FliD/sialyl-Lewisx mediated adhesion of Pseudomonas aeruginosa.
Résumé
: We have previously shown that the pro-inflammatory cytokine TNF (tumour necrosis factor) could drive sLex (sialyl-Lewisx) biosynthesis through the up-regulation of the BX transcript isoform of ST3GAL4 sialyltransferase gene in lung epithelial cells and human bronchial mucosa. Here, we show that the TNF-induced up-regulation of ST3GAL4 BX transcript is mediated by the mitogen and stress activated protein kinases MSK1/2 through Erk (extracellular signal-regulated kinase) and p38 MAPK (mitogen-activated protein kinase) pathways, and increases sLex expression on high molecular weight glycoproteins in the inflamed airway epithelium. We also show that the TNF-induced sLex expression increases the adhesion of Pseudomonas aeruginosa PAO1 and PAK strains to lung epithelial cells in a FliD-dependent manner. These results suggest that Erk and p38 MAPK, and the downstream kinase MSK1/2 should be considered as potential targets to hamper inflammation, bronchial mucins glycosylation changes and P. aeruginosa binding in the lung of patients suffering from lung diseases such as chronic bronchitis or cystic fibrosis.