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.

Andrographolide exerted its antimicrobial effects by upregulation of human β-defensin-2 induced through p38 MAPK and NF-κB pathway in human lung epithelial cells

2012 ◽  
Vol 90 (5) ◽  
pp. 647-653 ◽  
Author(s):  
Zhen-Jun Shao ◽  
Xiao-Wei Zheng ◽  
Ting Feng ◽  
Juan Huang ◽  
Jian Chen ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
P38 Mapk ◽  
Nuclear Factor Κb ◽  
Lung Epithelial Cells ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Antimicrobial Effects ◽  
Reverse Transcription Pcr ◽  
Lung Epithelial ◽  
Mitogen Activated Protein

Andrographis paniculata (Burm. f) Nees is a traditional herbal medicine for the treatment of infection and inflammation in China. Andrographolide (andro) is one of the major components. Human β-defensin-2 (hBD-2) is an inducible antimicrobial peptide that plays an important role in innate immunity. The present study aimed to investigate the effect of andro on upregulation of hBD-2 and the key signaling pathways involved in andro-induced hBD-2 expression. Real-time reverse transcription – PCR and Western blot assays showed that andro (1.0–10 µmol/L) can upregulate the expression of hBD-2 in a dose-dependent manner. Further studies suggested that hBD-2 mRNA and protein expression in responsive to andro were attenuated by pretreatment with SB203580 (an inhibitor of p38 mitogen-activated protein kinase (p38 MAPK)), MG-132 (an inhibitor of nuclear factor κB (NF-κB)), and an NF-κB activator inhibitor, but not by an inhibitor of ERK (PD98059) or by an inhibitor of JNK(SP600125). Moreover, we found that a second p38 MAPK inhibitor (SB202190) significantly blocked andro-mediated hBD-2 induction in SPC-A-1 lung epithelial cells. Finally, the p-c-Jun transcription factor activity assay also showed that AP-1 activity was induced by andro compared with the untreated group. We conclude that andro may exert its antimicrobial effects by upregulating the expression of hBD-2 through the p38 MAPK and NF-κB pathway.

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

scholarly journals p38mapk and MEK1/2 inhibition contribute to cellular oxidant injury after hypoxia

2004 ◽  
Vol 286 (4) ◽  
pp. L826-L833 ◽  
Author(s):  
Charles S. Powell ◽  
Marcienne M. Wright ◽  
Robert M. Jackson
Keyword(s):  
Epithelial Cells ◽  
Signaling Pathways ◽  
A549 Cells ◽  
Lung Epithelial Cells ◽  
Protective Effects ◽  
Hypoxia Exposure ◽  
Extracellular Signal ◽  
Lung Epithelial ◽  
Mitogen Activated Protein ◽  
Chemical Inhibition

Lung epithelial cells produce increased reactive oxygen species (ROS) after hypoxia exposure, and they are more susceptible after hypoxia to injury by agents that generate superoxide [[Formula: see text]; e.g., 2,3-dimethoxy-1,4-naphthoquinone (DMNQ)]. Cellular GSH and MnSOD both decrease in hypoxic lung epithelial cells, altering the redox state. Because ROS participate in signaling pathways involved in cell death or survival, we tested the hypothesis that mitogen-activated protein kinases (MAPK) were involved in a protective response against cellular injury during reoxygenation. Human lung epithelial A549 cells were incubated in hypoxia (<1% O2 for 24 h) and then reoxygenated by return to air. p38mapk and MKK3 phosphorylation both decreased after hypoxia. During reoxygenation, cells were incubated with DMNQ (0–50 μM), a redox cycling quinone that produces [Formula: see text]. Hypoxia preexposure significantly increased epithelial cell lysis resulting from DMNQ. Addition of the p38mapk inhibitors SB-202190 or SB-203580 markedly increased cytotoxicity, as did the mitogen/extracellular signal-regulated kinase (MEK) 1/2 inhibitor PD-98059 (all 10 μM), suggesting a protective effect of downstream molecules activated by the kinases. Transfection of A549 cells with a dominant active MKK3 plasmid (MKK3[Glu]) partially inhibited cytolysis resulting from DMNQ, whereas the inactive MKK3 plasmid (MKK3[Ala]) had less evident protective effects. Stress-related signaling pathways in epithelial cells are modulated by hypoxia and confer protection from reoxygenation, since hypoxia and chemical inhibition of p38mapk and MEK1/2 similarly increase cytolysis resulting from [Formula: see text].

scholarly journals Epithelial Adhesion Mediated by Pilin SpaC Is Required for Lactobacillus rhamnosus GG-Induced Cellular Responses

2014 ◽  
Vol 80 (16) ◽  
pp. 5068-5077 ◽  
Author(s):  
Courtney S. Ardita ◽  
Jeffrey W. Mercante ◽  
Young Man Kwon ◽  
Liping Luo ◽  
Madelyn E. Crawford ◽  
...  
Keyword(s):  
Lactobacillus Rhamnosus ◽  
Surface Protein ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Critical Surface ◽  
Content Type ◽  
Epithelial Migration ◽  
Extracellular Signal ◽  
Nadph Oxidase 1 ◽  
Mitogen Activated Protein

ABSTRACTLactobacillus rhamnosusGG is a widely used probiotic, and the strain's salutary effects on the intestine have been extensively documented. We previously reported that strain GG can modulate inflammatory signaling, as well as epithelial migration and proliferation, by activating NADPH oxidase 1-catalyzed generation of reactive oxygen species (ROS). However, how strain GG induces these responses is unknown. Here, we report that strain GG's probiotic benefits are dependent on the bacterial-epithelial interaction mediated by the SpaC pilin subunit. By comparing strain GG to an isogenic mutant that lacks SpaC (strain GGΩspaC), we establish that SpaC is necessary for strain GG to adhere to gut mucosa, that SpaC contributes to strain GG-induced epithelial generation of ROS, and that SpaC plays a role in strain GG's capacity to stimulate extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling in enterocytes. In addition, we show that SpaC is required for strain GG-mediated stimulation of cell proliferation and protection against radiologically inflicted intestinal injury. The identification of a critical surface protein required for strain GG to mediate its probiotic influence advances our understanding of the molecular basis for the symbiotic relationship between some commensal bacteria of the gut lumen and enterocytes. Further insights into this relationship are critical for the development of novel approaches to treat intestinal diseases.

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