PMID- 24099577 OWN - NLM STAT- MEDLINE DCOM- 20140307 LR - 20221207 IS - 1470-8728 (Electronic) IS - 0264-6021 (Linking) VI - 457 IP - 1 DP - 2014 Jan 1 TI - TNF induces the expression of the sialyltransferase ST3Gal IV in human bronchial mucosa via MSK1/2 protein kinases and increases FliD/sialyl-Lewis(x)-mediated adhesion of Pseudomonas aeruginosa. PG - 79-87 LID - 10.1042/BJ20130989 [doi] AB - We have shown previously that the pro-inflammatory cytokine TNF (tumour necrosis factor) could drive sLe(x) (sialyl-Lewis(x)) biosynthesis through the up-regulation of the BX transcript isoform of the ST3GAL4 (ST3 beta-galactoside alpha-2,3-sialyltransferase 4) sialyltransferase gene in lung epithelial cells and human bronchial mucosa. In the present study, we show that the TNF-induced up-regulation of the ST3GAL4 BX transcript is mediated by MSK1/2 (mitogen- and stress-activated kinase 1/2) through the ERK (extracellular-signal-regulated kinase) and p38 MAPK (mitogen-activated protein kinase) pathways, and increases sLe(x) expression on high-molecular-mass glycoproteins in inflamed airway epithelium. We also show that the TNF-induced sLe(x) expression increases the adhesion of the 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 mucin glycosylation changes and P. aeruginosa binding in the lung of patients suffering from lung diseases such as chronic bronchitis or cystic fibrosis. FAU - Colomb, Florent AU - Colomb F AD - *Universite Lille Nord de France, Lille 1, UGSF (Unite de Glycobiologie Structurale et Fonctionnelle), CNRS (Centre National de la Recherche Scientifique), UMR 8576, 59650 Villeneuve d'Ascq, France. FAU - Vidal, Olivier AU - Vidal O FAU - Bobowski, Marie AU - Bobowski M FAU - Krzewinski-Recchi, Marie-Ange AU - Krzewinski-Recchi MA FAU - Harduin-Lepers, Anne AU - Harduin-Lepers A FAU - Mensier, Eric AU - Mensier E FAU - Jaillard, Sophie AU - Jaillard S FAU - Lafitte, Jean-Jacques AU - Lafitte JJ FAU - Delannoy, Philippe AU - Delannoy P FAU - Groux-Degroote, Sophie AU - Groux-Degroote S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Biochem J JT - The Biochemical journal JID - 2984726R RN - 0 (Bacterial Proteins) RN - 0 (Oligosaccharides) RN - 0 (Sialyl Lewis X Antigen) RN - 0 (Tumor Necrosis Factor-alpha) RN - 147757-14-0 (FlaD protein, Bacteria) RN - EC 2.4.99.- (Sialyltransferases) RN - EC 2.7.11.1 (RPS6KA4 protein, human) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 90-kDa) RN - EC 2.7.11.1 (mitogen and stress-activated protein kinase 1) RN - EC 2.4.99.4 (beta-Galactoside alpha-2,3-Sialyltransferase) SB - IM MH - Bacterial Adhesion/*drug effects MH - Bacterial Proteins/physiology MH - Bronchi/drug effects/enzymology MH - Gene Expression Regulation, Enzymologic/drug effects MH - Humans MH - Oligosaccharides/physiology MH - Pseudomonas aeruginosa/*drug effects/physiology MH - Respiratory Mucosa/*drug effects/metabolism MH - Ribosomal Protein S6 Kinases, 90-kDa/*physiology MH - Sialyl Lewis X Antigen MH - Sialyltransferases/*genetics/metabolism MH - Tumor Cells, Cultured MH - Tumor Necrosis Factor-alpha/*pharmacology MH - Up-Regulation/drug effects MH - beta-Galactoside alpha-2,3-Sialyltransferase EDAT- 2013/10/09 06:00 MHDA- 2014/03/08 06:00 CRDT- 2013/10/09 06:00 PHST- 2013/10/09 06:00 [entrez] PHST- 2013/10/09 06:00 [pubmed] PHST- 2014/03/08 06:00 [medline] AID - BJ20130989 [pii] AID - 10.1042/BJ20130989 [doi] PST - ppublish SO - Biochem J. 2014 Jan 1;457(1):79-87. doi: 10.1042/BJ20130989.