TNF up-regulates ST3GAL4 and sialyl-Lewisx expression in lung epithelial cells through an intronic ATF2-responsive element.
We have previously shown that tumor necrosis factor (TNF) induced the up-regulation of the sialyltransferase gene ST3GAL4 (α2,3-sialyltransferase gene) BX transcript through mitogen- and stress-activated kinase 1/2 (MSK1/2), extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) signaling pathways. This up-regulation resulted in sialyl-Lewisx(sLex) overexpression on high-molecular-weight glycoproteins in inflamed airway epithelium and increased the adhesion of Pseudomonas aeruginosa PAO1 and PAK strains to lung epithelial cells. In the present study, we describe a TNF-responsive element in an intronic region of the ST3GAL4 gene, whose TNF-dependent activity is repressed by ERK/p38 and MSK1/2 inhibitors. This TNF-responsive element contains potential binding sites for ETS1 and ATF2 transcription factors related to TNF signaling. We also show that ATF2 is involved in TNF responsiveness, as well as in TNF-induced ST3GAL4 BX transcript and sLexoverexpression in A549 lung epithelial cells. Moreover, we show that TNF induces the binding of ATF2 to the TNF-responsive element. Altogether, these data suggest that ATF2 could be a potential target to prevent inflammation-induced P. aeruginosa binding in the lung of patients suffering from lung diseases such as chronic bronchitis or cystic fibrosis.
Université Lille, CNRS, UMR 8576, Unité de Glycobiologie Structurale etFonctionnelle (UGSF), F-59000 Lille, France.
Florent
F
Colomb
Université Lille, CNRS, UMR 8576, Unité de Glycobiologie Structurale etFonctionnelle (UGSF), F-59000 Lille, France.
Marie-Ange
MA
Krzewinski-Recchi
Université Lille, CNRS, UMR 8576, Unité de Glycobiologie Structurale etFonctionnelle (UGSF), F-59000 Lille, France.
Agata
A
Steenackers
Université Lille, Inserm, CHU Lille, UMR-S 1172, Jean-Pierre Aubert Research Center (JPARC), F-59000 Lille, France.
Audrey
A
Vincent
Université Lille, CNRS, UMR 8576, Unité de Glycobiologie Structurale etFonctionnelle (UGSF), F-59000 Lille, France.
Anne
A
Harduin-Lepers
Université Lille, CNRS, UMR 8576, Unité de Glycobiologie Structurale etFonctionnelle (UGSF), F-59000 Lille, France.
Philippe
P
Delannoy
Université Lille, CNRS, UMR 8576, Unité de Glycobiologie Structurale etFonctionnelle (UGSF), F-59000 Lille, France sophie.groux-degroote@univ-lille1.fr.
Sophie
S
Groux-Degroote
D000072283:A549 Cells; D051698:Activating Transcription Factor 2 / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D009844:Oligosaccharides / Q000096:biosynthesis*; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000378:metabolism; D020545:Respiratory Mucosa / Q000378:metabolism*; D020218:Response Elements; D000080506:Sialyl Lewis X Antigen; D012799:Sialyltransferases / Q000096:biosynthesis* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; C494041:ETS1 protein, human; D009844:Oligosaccharides; D050784:Proto-Oncogene Protein c-ets-1; D000080506:Sialyl Lewis X Antigen; D014409:Tumor Necrosis Factor-alpha; D012799:Sialyltransferases; D048049:Extracellular Signal-Regulated MAP Kinases; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
ATF2; inflammation; intronic element; sialyltransferase; transcriptional regulation