Neutrophil elastase induces IL-8 synthesis by lung epithelial cells via the mitogen-activated protein kinase pathway

2004 ◽  
Vol 11 (1) ◽  
pp. 49-58 ◽  
Author(s):  
Hao-Cheng Chen ◽  
Horng-Chyuan Lin ◽  
Chien-Ying Liu ◽  
Chun-Hua Wang ◽  
Tritium Hwang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Epithelial Cells ◽  
Neutrophil Elastase ◽  
Lung Epithelial Cells ◽  
Mitogen Activated Protein Kinase ◽  
Lung Epithelial ◽  
Mitogen Activated Protein ◽  
Kinase Pathway

TNF up-regulates ST3GAL4 and sialyl-Lewisx expression in lung epithelial cells through an intronic ATF2-responsive element

2016 ◽  
Vol 474 (1) ◽  
pp. 65-78 ◽  
Author(s):  
Florent Colomb ◽  
Marie-Ange Krzewinski-Recchi ◽  
Agata Steenackers ◽  
Audrey Vincent ◽  
Anne Harduin-Lepers ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mapk Signaling ◽  
Lung Epithelial Cells ◽  
Mitogen Activated Protein Kinase ◽  
Sialyl Lewisx ◽  
Extracellular Signal ◽  
Potential Binding ◽  
Lung Epithelial ◽  
Mitogen Activated Protein ◽  
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 sLex overexpression 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.

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