ArticleRespiratory research2024
CTSS contributes to airway neutrophilic inflammation in mixed granulocytic asthma.
Article in Respiratory research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Different Inflammatory Phenotypes and Immune Endotypes Drive Disease Heterogeneity in Asthma and COPD.Clinical reviews in allergy & immunology · 2026Review
- Cannabichromeorcin targets cathepsin L to alleviate oxidative stress-Driven airway inflammation in severe asthma.Redox biology · 2026Article
- Unveiling an ALS Blood Transcriptomic Signature: A Machine Learning Classifier Distinct from Neurodegenerative Controls.Neuroinformatics · 2026Article
- Monocyte-Derived LGMNResearch (Washington, D.C.) · 2026Article
- New insights into mesenchymal stem cells in inflammatory subtypes of asthma.Frontiers in immunology · 2025Review
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Authors and funding
14 authors.
Funding
Abstract
backgroundMixed granulocytic asthma (MGA) is usually associated with poor response to corticosteroid therapy and a high risk of severe asthma. Cathepsin S (CTSS) has been found to play an important role in various inflammatory diseases. This study was aimed to investigate the role of CTSS in MGA.
methodsInduced sputum was obtained from healthy subjects and asthma patients. Two murine models of MGA were established using either TDI (toluene diisocyanate) alone or OVA emulsified in CFA. LY3000328, a specific antagonist of CTSS, was therapeutically given to BALB/c mice after airway challenge with TDI or OVA. The effects of recombinant CTSS was tested in vivo, and Akt inhibition was used to explore a possible mechanism for CTSS-induced airway inflammation.
resultsMGA patients have a significant higher sputum CTSS level than the health and subjects with other inflammatory phenotypes, which was positively correlated with sputum level of soluble E-cadherin (sE-cadherin), sputum neutrophils, FeNO, FEF25-75% and glucocorticoid dosage. Allergen exposure markedly increased CTSS level and pharmacological antagonism of CTSS with LY3000328 decreased airway hyperresponsiveness, airway neutrophil accumulation, as well as the release of IL-17 and sE-cadherin in murine models of MGA, yet had no effects on eosinophilic inflammation nor type 2 inflammatory cytokines (IL-4 and IL-5). In addition, intratracheal instillation of recombinant CTSS leads to neutrophil recruitment and overproduction of sE-cadherin in the lung tissues, which could be attenuated by inhibition of Akt signaling.
conclusionOur data suggested that CTSS contributes to airway neutrophilic inflammation in MGA through an Akt-dependent pathway.
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