ArticleArthritis and rheumatism2013
Tumor necrosis factor α- and interleukin-1β-dependent induction of CCL3 expression by nucleus pulposus cells promotes macrophage migration through CCR1.
Article in Arthritis and rheumatism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
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Who cites it
120 citing papers in PubMed, 183 citations in OpenAlex.
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- Blood and lymphatic vascular remodeling in intervertebral disc degeneration.Frontiers in immunology · 2026Review
- Macrophage Subtypes Distinctly Impact Intervertebral Disc Inflammation and Extracellular Matrix Composition.JOR spine · 2025Article
- Value of contrast-enhanced MRI for predicting resorption of ruptured lumbar disc herniation: a prospective study of 82 cases.Journal of orthopaedic surgery and research · 2025Article
- Platelets induce endothelial cell mitochondrial dysfunction in myocardial infarction.Science advances · 2025Article
- Lung adenocarcinoma-derived IFN-γ promotes growth by modulating CD8+ T cell production of CCR5 chemokines.The Journal of clinical investigation · 2025Article
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- Role of Tumor Necrosis Factor in Tuberculosis.Biomolecules · 2025Review
- Pyroptosis: A spoiler of peaceful coexistence between cells in degenerative bone and joint diseases.Journal of advanced research · 2025Review
- The scRNA-sequencing landscape of pancreatic ductal adenocarcinoma revealed distinct cell populations associated with tumor initiation and progression.Genes & diseases · 2025Article
- Modic changes: From potential molecular mechanisms to future research directions (Review).Molecular medicine reports · 2025Review
- Article
60 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
objectiveTo investigate tumor necrosis factor α (TNFα) and interleukin-1β (IL-1β) regulation of CCL3 expression in nucleus pulposus (NP) cells and in macrophage migration.
methodsQuantitative reverse transcription-polymerase chain reaction and immunohistochemistry were used to measure CCL3 expression in NP cells. Transfections were used to determine the role of NF-κB, CCAAT/enhancer binding protein (C/EBPβ), and MAPK on cytokine-mediated CCL3 promoter activity. The effect of NP-conditioned medium on macrophage migration was measured using a Transwell system.
resultsAn increase in CCL3 expression and promoter activity was observed in NP cells after TNFα or IL-1β treatment. Treatment of cells with NF-κB and MAPK inhibitors abolished the effect of the cytokines on CCL3 expression. The inductive effect of p65 and C/EBPβ on the CCL3 promoter was confirmed through gain-of-function and loss-of-function studies. Notably, cotransfection with p50 completely blocked cytokine- and p65-dependent induction. In contrast, c-Rel and RelB had little effect on promoter activity. Lentiviral transduction with short hairpin RNA for p65 (shp65) and shIKKβ significantly decreased the TNFα-dependent increase in CCL3 expression. Analysis of degenerated human NP tissue samples showed that CCL3, but not CCL4, expression correlated positively with the grade of tissue degeneration. Importantly, treatment of macrophages with conditioned medium of NP cells treated with TNFα or IL-1β promoted their migration. Pretreatment of macrophages with an antagonist of CCR1, the primary receptor for CCL3 and CCL4, blocked cytokine-mediated migration.
conclusionOur findings indicate that TNFα and IL-1β modulate the expression of CCL3 in NP cells by controlling the activation of MAPK, NF-κB, and C/EBPβ signaling. The CCL3-CCR1 axis may play an important role in promoting macrophage infiltration in degenerated, herniated discs.
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