ArticleInternational journal of molecular sciences2017
Glycosaminoglycans Regulate CXCR3 Ligands at Distinct Levels: Protection against Processing by Dipeptidyl Peptidase IV/CD26 and Interference with Receptor Signaling.
Article in International journal of molecular sciences, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Chemokines in the resolution of inflammation: key players and targets for therapeutic modulation.Frontiers in immunology · 2025Review
- Natural carboxyterminal truncation of human CXCL10 attenuates glycosaminoglycan binding, CXCR3A signaling and lymphocyte chemotaxis, while retaining angiostatic activity.Cell communication and signaling : CCS · 2024Article
- Protection of stromal cell-derived factor-1 SDF-1/CXCL12 against proteases yields improved skin wound healing.Frontiers in immunology · 2024Article
- Chemokines form complex signals during inflammation and disease that can be decoded by extracellular matrix proteoglycans.Science signaling · 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 GAG-Binding Peptide MIG30 Protects against Liver Ischemia-Reperfusion in Mice.International journal of molecular sciences · 2022Article
- Targeting of Glycosaminoglycans in Genetic and Inflammatory Airway Disease.International journal of molecular sciences · 2022Review
- Role of extracellular matrix proteoglycans in immune cell recruitment.International journal of experimental pathology · 2022Review
- Inhibition of renal fibrosis with a human CXCL9-derived glycosaminoglycan-binding peptide.Clinical & translational immunology · 2022Article
- Review
- A model of the innate immune response to SARS-CoV-2 in the alveolar epithelium.Royal Society open science · 2021Article
- Perspectives on the Biological Role of Chemokine:Glycosaminoglycan Interactions.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2021Review
- Understanding the mechanisms that facilitate specificity, not redundancy, of chemokine-mediated leukocyte recruitment.Immunology · 2020Review
- Favorable Immune Microenvironment in Patients with EGFR and MAPK Co-Mutations.Lung Cancer (Auckland, N.Z.) · 2020Article
- Targeting Chemokine-Glycosaminoglycan Interactions to Inhibit Inflammation.Frontiers in immunology · 2020Review
- Differential Effects of Posttranslational Modifications of CXCL8/Interleukin-8 on CXCR1 and CXCR2 Internalization and Signaling Properties.International journal of molecular sciences · 2018Article
- Neutrophils: Beneficial and Harmful Cells in Septic Arthritis.International journal of molecular sciences · 2018Review
- Peroxynitrite Exposure of CXCL12 Impairs Monocyte, Lymphocyte and Endothelial Cell Chemotaxis, Lymphocyte ExtravasationFrontiers in immunology · 2018Article
- Regulation of Chemokine-Receptor Interactions and Functions.International journal of molecular sciences · 2017Article
- Overview of the Mechanisms that May Contribute to the Non-Redundant Activities of Interferon-Inducible CXC Chemokine Receptor 3 Ligands.Frontiers in immunology · 2017Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CXC chemokine ligand (CXCL)9, CXCL10 and CXCL11 direct chemotaxis of mainly T cells and NK cells through activation of their common CXC chemokine receptor (CXCR)3. They are inactivated upon NH₂-terminal cleavage by dipeptidyl peptidase IV/CD26. In the present study, we found that different glycosaminoglycans (GAGs) protect the CXCR3 ligands against proteolytic processing by CD26 without directly affecting the enzymatic activity of CD26. In addition, GAGs were shown to interfere with chemokine-induced CXCR3 signaling. The observation that heparan sulfate did not, and heparin only moderately, altered CXCL10-induced T cell chemotaxis in vitro may be explained by a combination of protection against proteolytic inactivation and altered receptor interaction as observed in calcium assays. No effect of CD26 inhibition was found on CXCL10-induced chemotaxis in vitro. However, treatment of mice with the CD26 inhibitor sitagliptin resulted in an enhanced CXCL10-induced lymphocyte influx into the joint. This study reveals a dual role for GAGs in modulating the biological activity of CXCR3 ligands. GAGs protect the chemokines from proteolytic cleavage but also directly interfere with chemokine-CXCR3 signaling. These data support the hypothesis that both GAGs and CD26 affect the in vivo chemokine function.
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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.