ArticleBioscience reports2013
Designing CXCL8-based decoy proteins with strong anti-inflammatory activity in vivo.
Article in Bioscience reports, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
- Glycosaminoglycan binding to soluble CX3CL1 impacts monocyte migrationFrontiers in immunology · 2026Article
- Immunogenicity of a CXCL8-based biopharmaceutical drug candidate in comparison to its wildtype form.Frontiers in immunology · 2025Article
- Designing a CXCL8-hsa chimera as potential immunmodulator of the tumor micro-environment.Frontiers in immunology · 2025Article
- Chemokine Binding to Tenascin-C Influences Chemokine-Induced Immune Cell Migration.International journal of molecular sciences · 2023Article
- Microenvironmental control of hematopoietic stem cell fate via CXCL8 and protein kinase C.Cell reports · 2023Article
- Chemokines and chemokine receptors as promising targets in rheumatoid arthritis.Frontiers in immunology · 2023Review
- The GAG-Binding Peptide MIG30 Protects against Liver Ischemia-Reperfusion in Mice.International journal of molecular sciences · 2022Article
- The Role of Heparan Sulfate in CCL26-Induced Eosinophil Chemotaxis.International journal of molecular sciences · 2022Article
- Isolation and Characterization of Heparan Sulfate from Human Lung Tissues.Molecules (Basel, Switzerland) · 2021Article
- Location, location, location: how the tissue microenvironment affects inflammation in RA.Nature reviews. Rheumatology · 2021Review
- Targeting Chemokine-Glycosaminoglycan Interactions to Inhibit Inflammation.Frontiers in immunology · 2020Review
- A C-terminal CXCL8 peptide based on chemokine-glycosaminoglycan interactions reduces neutrophil adhesion and migration during inflammation.Immunology · 2019Article
- A Requirement for Neutrophil Glycosaminoglycans in Chemokine:Receptor Interactions Is Revealed by the Streptococcal Protease SpyCEP.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Novel Anti-Inflammatory Peptides Based on Chemokine-Glycosaminoglycan Interactions Reduce Leukocyte Migration and Disease Severity in a Model of Rheumatoid Arthritis.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Glycosaminoglycan Interactions with Chemokines Add Complexity to a Complex System.Pharmaceuticals (Basel, Switzerland) · 2017Review
- Regulation of Chemokine Function: The Roles of GAG-Binding and Post-Translational Nitration.International journal of molecular sciences · 2017Review
- Structural Analysis of Chemokine Receptor-Ligand Interactions.Journal of medicinal chemistry · 2017Review
- CXCL9-Derived Peptides Differentially Inhibit Neutrophil MigrationFrontiers in immunology · 2017Article
- The Positively Charged COOH-terminal Glycosaminoglycan-binding CXCL9(74-103) Peptide Inhibits CXCL8-induced Neutrophil Extravasation and Monosodium Urate Crystal-induced Gout in Mice.The Journal of biological chemistry · 2015Article
- A combinatorial approach to biophysically characterise chemokine-glycan binding affinities for drug development.Molecules (Basel, Switzerland) · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
IL (interleukin)-8 [CXCL8 (CXC chemokine ligand 8)] exerts its role in inflammation by triggering neutrophils via its specific GPCRs (G-protein-coupled receptors), CXCR1 (CXC chemokine receptor 1) and CXCR2, for which additional binding to endothelial HS-GAGs (heparan sulphate-glycosaminoglycans) is required. We present here a novel approach for blocking the CXCL8-related inflammatory cascade by generating dominant-negative CXCL8 mutants with improved GAG-binding affinity and knocked-out CXCR1/CXCR2 activity. These non-signalling CXCL8 decoy proteins are able to displace WT (wild-type) CXCL8 and to prevent CXCR1/CXCR2 signalling thereby interfering with the inflammatory response. We have designed 14 CXCL8 mutants that we subdivided into three classes according to number and site of mutations. The decoys were characterized by IFTs (isothermal fluorescence titrations) and SPR (surface plasmon resonance) to determine GAG affinity. Protein stability and structural changes were evaluated by far-UV CD spectroscopy and knocked-out GPCR response was shown by Boyden chamber and Ca2+ release assays. From these experiments, CXCL8(Δ6F17KF21KE70KN71K) emerged with the most promising in vitro characteristics. This mutant was therefore further investigated in a murine model of mBSA (methylated BSA)-induced arthritis in mice where it showed strong anti-inflammatory activity. Based on these results, we propose that dominant-negative CXCL8 decoy proteins are a promising class of novel biopharmaceuticals with high therapeutic potential in inflammatory diseases.
Indexed as
Identifiers
What OpenQuestion holds
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.