Related Experiment Video
Updated: Sep 3, 2025
Studying Effects of Cigarette Smoke on Pseudomonas Infection in Lung Epithelial Cells
Published on: May 11, 2020
Pseudomonas aeruginosa Alters Critical Lung Epithelial Cell Functions through Activation of ADAM17
Ahmad Aljohmani1, Noah Niklas Andres1, Daniela Yildiz1
1Institute of Experimental and Clinical Pharmacology and Toxicology, PZMS, ZHMB, Saarland University, 66421 Homburg, Germany.
Abstract:
Severe epithelial dysfunction is one major hallmark throughout the pathophysiological progress of bacterial pneumonia. Junctional and cellular adhesion molecules (e.g., JAMA-A, ICAM-1), cytokines (e.g., TNFα), and growth factors (e.g., TGFα), controlling proper lung barrier function and leukocyte recruitment, are proteolytically cleaved and released into the extracellular space through a disintegrin and metalloproteinase (ADAM) 17. In cell-based assays, we could show that the protein expression, maturation, and activation of ADAM17 is upregulated upon infection of lung epithelial cells with Pseudomonas aeruginosa and Exotoxin A (ExoA), without any impact of infection by Streptococcus pneumoniae. The characterization of released extracellular vesicles/exosomes and the comparison to heat-inactivated bacteria revealed that this increase occurred in a cell-associated and toxin-dependent manner. Pharmacological targeting and gene silencing of ADAM17 showed that its activation during infection with Pseudomonas aeruginosa was critical for the cleavage of junctional adhesion molecule A (JAM-A) and epithelial cell survival, both modulating barrier integrity, epithelial regeneration, leukocyte adhesion and transepithelial migration. Thus, site-specific targeting of ADAM17 or blockage of the activating toxins may constitute a novel anti-infective therapeutic option in Pseudomonas aeruginosa lung infection preventing severe epithelial and organ dysfunctions and stimulating future translational studies.
Insights
Pseudomonas aeruginosa infection upregulates ADAM17, a key enzyme in bacterial pneumonia. Targeting ADAM17 or its toxins may offer new treatments for lung infections by protecting epithelial cells and barrier function.
Area of Science:
- Bacterial Pathogenesis
- Molecular Biology
- Pulmonary Medicine
Background:
- Severe epithelial dysfunction is a hallmark of bacterial pneumonia.
- ADAM17 cleaves adhesion molecules, cytokines, and growth factors, impacting lung barrier function and leukocyte recruitment.
Purpose of the Study:
- To investigate the role of ADAM17 in Pseudomonas aeruginosa lung infection.
- To determine if ADAM17 activation is critical for epithelial cell survival and barrier integrity during infection.
Main Methods:
- Cell-based assays using lung epithelial cells infected with Pseudomonas aeruginosa and Streptococcus pneumoniae.
- Analysis of ADAM17 protein expression, maturation, and activation.
- Pharmacological targeting and gene silencing of ADAM17.
- Characterization of extracellular vesicles and exosomes.
Main Results:
- ADAM17 expression, maturation, and activation were upregulated by Pseudomonas aeruginosa and Exotoxin A, but not Streptococcus pneumoniae.
- ADAM17 activation was cell-associated and toxin-dependent.
- Targeting ADAM17 was critical for junctional adhesion molecule A (JAM-A) cleavage and epithelial cell survival.
- ADAM17 modulated barrier integrity, epithelial regeneration, leukocyte adhesion, and transepithelial migration.
Conclusions:
- ADAM17 plays a critical role in Pseudomonas aeruginosa-induced lung epithelial dysfunction.
- Targeting ADAM17 or its activating toxins presents a potential therapeutic strategy for Pseudomonas aeruginosa lung infections.
- Further translational studies are warranted to explore ADAM17-targeted therapies.
