ArticleThe Journal of biological chemistry2011
Pulmonary proteases in the cystic fibrosis lung induce interleukin 8 expression from bronchial epithelial cells via a heme/meprin/epidermal growth factor receptor/Toll-like receptor pathway.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 62 citations in OpenAlex.
- Macrophage metabolism in inflammatory heart disease: new insights and therapeutic implications.Frontiers in medicine · 2025Review
- Analysis and prediction of interactions between transmembrane and non-transmembrane proteins.BMC genomics · 2024Article
- Lung microhaemorrhage drives oxidative/inflammatory damage in αERJ open research · 2023Article
- Diagnosis and Management of Cystic Fibrosis Exacerbations.Seminars in respiratory and critical care medicine · 2023Review
- Targeting of Glycosaminoglycans in Genetic and Inflammatory Airway Disease.International journal of molecular sciences · 2022Review
- Neutrophil Elastase Deficiency Ameliorates Myocardial Injury Post Myocardial Infarction in Mice.International journal of molecular sciences · 2021Article
- Epithelial Barrier Dysfunction in Chronic Respiratory Diseases.Frontiers in physiology · 2021Review
- Neutrophil Adaptations upon Recruitment to the Lung: New Concepts and Implications for Homeostasis and Disease.International journal of molecular sciences · 2020Review
- Glycosaminoglycans as Multifunctional Anti-Elastase and Anti-Inflammatory Drugs in Cystic Fibrosis Lung Disease.Frontiers in pharmacology · 2020Review
- Impaired Airway Epithelial Barrier Integrity in Response toFrontiers in immunology · 2020Article
- The Multifaceted Effects of Alpha1-Antitrypsin on Neutrophil Functions.Frontiers in pharmacology · 2018Review
- Mesenchymal Stem Cell Soluble Mediators and Cystic Fibrosis.Journal of stem cell research & therapy · 2017Article
- Autoinducer-2 FacilitatesFrontiers in microbiology · 2017Article
- Iron Acquisition Mechanisms and Their Role in the Virulence ofFrontiers in cellular and infection microbiology · 2017Review
- Toll-Like Receptors in Cystic Fibrosis: Impact of Dysfunctional microRNA on Innate Immune Responses in the Cystic Fibrosis Lung.Journal of innate immunity · 2016Review
- The Role of Short-Chain Fatty Acids, Produced by Anaerobic Bacteria, in the Cystic Fibrosis Airway.American journal of respiratory and critical care medicine · 2015Article
- Transcription of Interleukin-8: How Altered Regulation Can Affect Cystic Fibrosis Lung Disease.Biomolecules · 2015Review
- Pyocyanina contributory factor in haem acquisition and virulence enhancement of Porphyromonas gingivalis in the lung [corrected].PloS one · 2015Article
- MicroRNA Dysregulation in Cystic Fibrosis.Mediators of inflammation · 2015Review
- Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A high intrapulmonary protease burden is characteristic of cystic fibrosis (CF), and the resulting dysregulation of the protease/anti-protease balance has serious implications for inflammation in the CF lung. Because of this inflammation, micro-bleeds can occur releasing hemoglobin into the lung. The aim of this study was to investigate the effect of the protease-rich environment of the CF lung on human hemoglobin and to assess the proinflammatory effect of heme on CF bronchial epithelium. Here, we show that the Pseudomonas proteases (Pseudomonas elastase and alkaline protease) and the neutrophil proteases (neutrophil elastase (NE) and proteinase-3) are capable of almost complete degradation of hemoglobin in vitro but that NE is the predominant protease that cleaves hemoglobin in vivo in CF bronchoalveolar lavage fluid. One of the effects of this is the release of heme, and in this study we show that heme stimulates IL-8 and IL-10 protein production from ΔF508 CFBE41o(-) bronchial epithelial cells. In addition, heme-induced IL-8 expression utilizes a novel pathway involving meprin, EGF receptor, and MyD88. Meprin levels are elevated in CF cell lines and bronchial brushings, thus adding to the proinflammatory milieu. Interestingly, α(1)-antitrypsin, in addition to its ability to neutralize NE and protease-3, can also bind heme and neutralize heme-induced IL-8 from CFBE41o(-) cells. This study illustrates the proinflammatory effects of micro-bleeds in the CF lung, the process by which this occurs, and a potential therapeutic intervention.
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