ArticleThe Journal of biological chemistry2016
Neutrophilic Cathepsin C Is Maturated by a Multistep Proteolytic Process and Secreted by Activated Cells during Inflammatory Lung Diseases.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 66 citations in OpenAlex.
- Dipeptidyl Peptidase 1 Inhibitor AZD7986 Induces a Sustained, Exposure-Dependent Reduction in Neutrophil Elastase Activity in Healthy Subjects.Clinical pharmacology and therapeutics · 2018Trial
- Targeting Cathepsin C in Cancer Metastasis: Protease Network Activation, Inflammatory Crosstalk, and Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Impact of dipeptidyl peptidase I and neutrophil serine proteases on neutrophil functional responses.Frontiers in pharmacology · 2026Article
- Inhibition of Airway Epithelial CTSC Attenuates Type 2 Inflammation: Implications for Eosinophilic Chronic Rhinosinusitis with Nasal Polyps.Journal of inflammation research · 2026Article
- Review
- Extracellular matrix anchored neutrophils drive pulmonary fibrosis in mice.Nature communications · 2025Article
- It's a Trap!-Potential of Cathepsins in NET Formation.International journal of molecular sciences · 2025Review
- Identification of Marrubiin as a Cathepsin C Inhibitor for Treating Rheumatoid Arthritis.Molecules (Basel, Switzerland) · 2025Article
- Dipeptidyl peptidase 1 inhibitors and neutrophilic inflammation in bronchiectasis: a narrative review.Journal of thoracic disease · 2025Review
- Exploring the involvement of serine proteases in neutrophil extracellular traps: a review of mechanisms and implications.Cell death & disease · 2025Review
- Exploring the roles of airway dipeptidyl peptidase 1 in obstructive airway disease.ERJ open research · 2025Article
- Dipeptidyl peptidase-1 inhibitors in bronchiectasis.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- PKM2 orchestrates tumor progression via metabolic reprogramming and MDSCs-mediated immune suppression in the tumor microenvironment.Frontiers in immunology · 2025Review
- Beyond the present: current and future perspectives on the role of infections in pediatric PCD.Frontiers in pediatrics · 2025Review
- Cathepsin C in health and disease: from structural insights to therapeutic prospects.Journal of translational medicine · 2024Review
- Biomarkers in bronchiectasis.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- Neutrophil-Derived Proteases in Lung Inflammation: Old Players and New Prospects.International journal of molecular sciences · 2024Review
- Cathepsin C regulates tumor progression via the Yes-associated protein signaling pathway in non-small cell lung cancer.American journal of cancer research · 2024Article
- The Role of Cysteine Protease Cathepsins B, H, C, and X/Z in Neurodegenerative Diseases and Cancer.International journal of molecular sciences · 2023Review
- Development and validation of asthma risk prediction models using co-expression gene modules and machine learning methods.Scientific reports · 2023Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cysteine protease cathepsin C (CatC) activates granule-associated proinflammatory serine proteases in hematopoietic precursor cells. Its early inhibition in the bone marrow is regarded as a new therapeutic strategy for treating proteolysis-driven chronic inflammatory diseases, but its complete inhibition is elusive in vivo Controlling the activity of CatC may be achieved by directly inhibiting its activity with a specific inhibitor or/and by preventing its maturation. We have investigated immunochemically and kinetically the occurrence of CatC and its proform in human hematopoietic precursor cells and in differentiated mature immune cells in lung secretions. The maturation of proCatC obeys a multistep mechanism that can be entirely managed by CatS in neutrophilic precursor cells. CatS inhibition by a cell-permeable inhibitor abrogated the release of the heavy and light chains from proCatC and blocked ∼80% of CatC activity. Under these conditions the activity of neutrophil serine proteases, however, was not abolished in precursor cell cultures. In patients with neutrophilic lung inflammation, mature CatC is found in large amounts in sputa. It is secreted by activated neutrophils as confirmed through lipopolysaccharide administration in a nonhuman primate model. CatS inhibitors currently in clinical trials are expected to decrease the activity of neutrophilic CatC without affecting those of elastase-like serine proteases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.