ArticleThe Journal of biological chemistry2015
Cysteine Cathepsins Activate ELR Chemokines and Inactivate Non-ELR Chemokines.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- Interruption of Endolysosomal Trafficking After Focal Brain Ischemia.Frontiers in molecular neuroscience · 2021Pooled it
- PRTN3 drives immunosuppression in KRAS-mutant lung adenocarcinoma through proteolytic inactivation of CXCL9.Journal for immunotherapy of cancer · 2026Article
- Cathepsin L as a Driver of Tumour Invasion and a Novel Therapeutic Target in Ovarian Cancer.Cancers · 2026Review
- Suppression of CSF2RA macrophage polarisation impacts pathological cardiac remodelling in mice.Scientific reports · 2026Article
- It's a Trap!-Potential of Cathepsins in NET Formation.International journal of molecular sciences · 2025Review
- Lysosome stress response and mitochondria injury are the earliest detectable alteration in FSGS.Scientific reports · 2025Article
- Cathepsins: Emerging targets in the tumor ecosystem to overcome cancers.Seminars in cancer biology · 2025Review
- Heterogeneous neutrophils in lung transplantation and proteolytic CXCL8 activation in COVID-19, influenza and lung transplant patient lungs.Cellular and molecular life sciences : CMLS · 2024Article
- MicroRNA-375 modulates neutrophil chemotaxis via targeting Cathepsin B in zebrafish.Fish & shellfish immunology · 2024Article
- Neutrophil-Derived Proteases in Lung Inflammation: Old Players and New Prospects.International journal of molecular sciences · 2024Review
- Unveiling the Potent Fibrino(geno)lytic, Anticoagulant, and Antithrombotic Effects of Papain, a Cysteine Protease fromInternational journal of molecular sciences · 2023Article
- A review of the pleiotropic actions of the IFN-inducible CXC chemokine receptor 3 ligands in the synovial microenvironment.Cellular and molecular life sciences : CMLS · 2023Review
- The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention.Cellular & molecular immunology · 2023Review
- Article
- Diagnostic value of serum cathepsin S in type 2 diabetic kidney disease.Frontiers in endocrinology · 2023Article
- Changes in chemokine and growth factor levels may be useful biomarkers for monitoring disease severity in COVID-19 patients; a pilot study.Frontiers in immunology · 2023Article
- Inhibition of anti-tumor immunity by melanoma cell-derived Activin-A depends on STING.Frontiers in immunology · 2023Article
- CTSB is a negative prognostic biomarker and therapeutic target associated with immune cells infiltration and immunosuppression in gliomas.Scientific reports · 2022Article
- Helicobacter pylori and gastric cancer: a lysosomal protease perspective.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2022Review
- Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Cysteine cathepsins are primarily lysosomal proteases involved in general protein turnover, but they also have specific proteolytic functions in antigen presentation and bone remodeling. Cathepsins are most stable at acidic pH, although growing evidence indicates that they have physiologically relevant activity also at neutral pH. Post-translational proteolytic processing of mature chemokines is a key, yet underappreciated, level of chemokine regulation. Although the role of selected serine proteases and matrix metalloproteases in chemokine processing has long been known, little has been reported about the role of cysteine cathepsins. Here we evaluated cleavage of CXC ELR (CXCL1, -2, -3, -5, and -8) and non-ELR (CXCL9-12) chemokines by cysteine cathepsins B, K, L, and S at neutral pH by high resolution Tris-Tricine SDS-PAGE and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Whereas cathepsin B cleaved chemokines especially in the C-terminal region, cathepsins K, L, and S cleaved chemokines at the N terminus with glycosaminoglycans modulating cathepsin processing of chemokines. The functional consequences of the cleavages were determined by Ca(2+) mobilization and chemotaxis assays. We show that cysteine cathepsins inactivate and in some cases degrade non-ELR CXC chemokines CXCL9-12. In contrast, cathepsins specifically process ELR CXC chemokines CXCL1, -2, -3, -5, and -8 N-terminally to the ELR motif, thereby generating agonist forms. This study suggests that cysteine cathepsins regulate chemokine activity and thereby leukocyte recruitment during protective or pathological inflammation.
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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.