ArticleThe Journal of biological chemistry2012
A chemokine receptor CXCR2 macromolecular complex regulates neutrophil functions in inflammatory diseases.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
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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
50 citing papers in PubMed, 85 citations in OpenAlex.
- Clinical Association of Chemokine (C-X-C motif) Ligand 1 (CXCL1) with Interstitial Pneumonia with Autoimmune Features (IPAF).Scientific reports · 2016Trial
- Curcumin Retains Anti-Inflammatory Effects Despite IDO Inhibition-Associated Neutrophilic Shift in OVA-Induced Rat Model.Biomolecules · 2026Article
- Nucleotide signaling in neutrophils: a key player in cancer dynamics.Purinergic signalling · 2026Review
- Gentamicin-Loaded Carbonate Apatite with Dual Antibacterial and Osteogenic Functions for Combating Surgical Site Infections.Advanced healthcare materials · 2026Article
- Dracorhodin perchlorate alleviates sciatic nerve pain in CCI rats by modulating inflammation and promoting nerve repair.Scientific reports · 2025Article
- Article
- Single-cell spatial analysis with Xenium reveals anti-tumour responses of CXCL13 + T and CXCL9+ cells after radiotherapy combined with anti-PD-L1 therapy.British journal of cancer · 2025Article
- Targeting CXCR2 signaling in inflammatory lung diseases: neutrophil-driven inflammation and emerging therapies.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- P2 purinergic receptor expression and function in tumor-related immune cells.Purinergic signalling · 2025Review
- Immunomodulatory Mechanisms of Rehmanniae Radix Praeparata-Achyranthes Root-Chinese Angelica Root Combination in Nontraumatic Osteonecrosis of the Femoral Head: A Comprehensive Network Pharmacology and Molecular Docking Study Focusing on Immunological Pathways.Mediators of inflammation · 2025Article
- Directing B7-H3 chimeric antigen receptor T cell homing through IL-8 induces potent antitumor activity against pediatric sarcoma.Journal for immunotherapy of cancer · 2024Article
- The Clinical Significance and Involvement in Molecular Cancer Processes of Chemokine CXCL1 in Selected Tumors.International journal of molecular sciences · 2024Review
- Neutrophils in Inflammatory Diseases: Unraveling the Impact of Their Derived Molecules and Heterogeneity.Cells · 2023Review
- SMYD2 regulates vascular smooth muscle cell phenotypic switching and intimal hyperplasia via interaction with myocardin.Cellular and molecular life sciences : CMLS · 2023Article
- Coronavirus Porcine Epidemic Diarrhea Virus Utilizes Chemokine Interleukin-8 to Facilitate Viral Replication by Regulating CaJournal of virology · 2023Article
- SMYD2 Regulates Vascular Smooth Muscle Cell Phenotypic Switching and Intimal Hyperplasia via Interaction with Myocardin.Research square · 2023Article
- CXCR2 Antagonist RIST4721 Acts as a Potent Chemotaxis Inhibitor of Mature Neutrophils Derived from Ex Vivo-Cultured Mouse Bone Marrow.Biomedicines · 2023Article
- White adipose tissue-derived factors and prostate cancer progression: mechanisms and targets for interventions.Cancer metastasis reviews · 2022Review
- Inhibition of BTK and PI3Kδ impairs the development of human JMML stem and progenitor cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- CXCR2 Receptor: Regulation of Expression, Signal Transduction, and Involvement in Cancer.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Inflammation plays an important role in a wide range of human diseases such as ischemia-reperfusion injury, arteriosclerosis, cystic fibrosis, inflammatory bowel disease, etc. Neutrophilic accumulation in the inflamed tissues is an essential component of normal host defense against infection, but uncontrolled neutrophilic infiltration can cause progressive damage to the tissue epithelium. The CXC chemokine receptor CXCR2 and its specific ligands have been reported to play critical roles in the pathophysiology of various inflammatory diseases. However, it is unclear how CXCR2 is coupled specifically to its downstream signaling molecules and modulates cellular functions of neutrophils. Here we show that the PDZ scaffold protein NHERF1 couples CXCR2 to its downstream effector phospholipase C (PLC)-β2, forming a macromolecular complex, through a PDZ-based interaction. We assembled a macromolecular complex of CXCR2·NHERF1·PLC-β2 in vitro, and we also detected such a complex in neutrophils by co-immunoprecipitation. We further observed that the CXCR2-containing macromolecular complex is critical for the CXCR2-mediated intracellular calcium mobilization and the resultant migration and infiltration of neutrophils, as disrupting the complex with a cell permeant CXCR2-specific peptide (containing the PDZ motif) inhibited intracellular calcium mobilization, chemotaxis, and transepithelial migration of neutrophils. Taken together, our data demonstrate a critical role of the PDZ-dependent CXCR2 macromolecular signaling complex in regulating neutrophil functions and suggest that targeting the CXCR2 multiprotein complex may represent a novel therapeutic strategy for certain inflammatory diseases.
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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.