ArticleThe American journal of pathology2018
Fibroblasts Promote Inflammation and Pain via IL-1α Induction of the Monocyte Chemoattractant Chemokine (C-C Motif) Ligand 2.
Article in The American journal of pathology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 40 citations in OpenAlex.
- Integrated single-cell and spatial transcriptomics reveal stromal-immune-vascular crosstalk in patients with interstitial cystitis/bladder pain syndrome.Experimental & molecular medicine · 2026Article
- Dermal fibroblast mitochondrial profiles in painful diabetic neuropathy.Diabetologia · 2026Article
- Dysplastic Epithelial Repair Propagates Chronic Pathology Through the Paracrine Transformation of Pulmonary Fibroblasts.bioRxiv : the preprint server for biology · 2026Article
- Pilonidal pit fibroblasts release cytokines that differ by sex and are altered by estrogen.Pediatric surgery international · 2026Article
- Histological and Immunohistochemical Characterization of the Tibial ACL Remnant: Implications for Ligament Healing.Medicina (Kaunas, Lithuania) · 2026Article
- An intricate relationship between fibrosis and autoimmune diseases: a specific focus on unraveling its molecular, immunological, and epigenetic drivers.Frontiers in immunology · 2026Review
- Unraveling the pleiotropic effects of CCR2-dependent signal transduction in fibrosis development.Theranostics · 2026Review
- Not Just Neurons: Pain Is Orchestrated in Partnership with Many Non-neuronal Cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- Macrophage migration inhibitory factor mediates joint capsule fibrosis via facilitating phospholipid metabolite PGE2 production in fibroblasts.Cellular and molecular life sciences : CMLS · 2025Article
- Fibroblast-Mediated Macrophage Recruitment Supports Acute Wound Healing.The Journal of investigative dermatology · 2025Article
- The axis of tumor-associated macrophages, extracellular matrix proteins, and cancer-associated fibroblasts in oncogenesis.Cancer cell international · 2024Review
- Deep skin fibroblast-mediated macrophage recruitment supports acute wound healing.bioRxiv : the preprint server for biology · 2024Article
- Expression of macrophage activation‑specific factors in hyperplastic scar tissue during hyperplasia phase by antibody array blotting membrane assay and its clinical significance.Experimental and therapeutic medicine · 2024Article
- Harmonizing hope: navigating the osteoarthritis melody through the CCL2/CCR2 axis for innovative therapeutic avenues.Frontiers in immunology · 2024Review
- Distinct fibroblast functions associated with fibrotic and immune-mediated inflammatory diseases and their implications for therapeutic development.F1000Research · 2024Review
- The Role of Inflammation-Associated Factors in Head and Neck Squamous Cell Carcinoma.Journal of inflammation research · 2023Review
- The Antioxidant and In Vitro Wound Healing Activity ofInternational journal of molecular sciences · 2022Article
- Effectiveness of Osteopathic Treatment on the Spinal Column as Measured by the Spinal Mouse®: A Case Series.Cureus · 2022Article
- Promising results of captopril in improving knee arthrofibrosis and cartilage status: an animal model study.Journal of experimental orthopaedics · 2022Article
- Optimization of the Duration and Dose of Photobiomodulation Therapy (660 nm Laser) for Spinal Cord Injury in Rats.Photobiomodulation, photomedicine, and laser surgery · 2022Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Fibroblasts persist within fibrotic scar tissue and exhibit considerable phenotypic and functional plasticity. Herein, we hypothesized that scar-associated fibroblasts may be a source of stress-induced inflammatory exacerbations and pain. To test this idea, we used a human model of surgery-induced fibrosis, total knee arthroplasty (TKA). Using a combination of tissue protein expression profiling and bioinformatics, we discovered that many months after TKA, the fibrotic joint exists in a state of unresolved chronic inflammation. Moreover, the infrapatellar fat pad, a soft tissue that becomes highly fibrotic in the post-TKA joint, expresses multiple inflammatory mediators, including the monocyte chemoattractant, chemokine (C-C motif) ligand (CCL) 2, and the innate immune trigger, IL-1α. Fibroblasts isolated from the post-TKA fibrotic infrapatellar fat pad express the IL-1 receptor and on exposure to IL-1α polarize to a highly inflammatory state that enables them to stimulate the recruitment of monocytes. Blockade of fibroblast CCL2 or its transcriptional regulator NF-κB prevented IL-1α-induced monocyte recruitment. Clinical investigations discovered that levels of patient-reported pain in the post-TKA joint correlated with concentrations of CCL2 in the joint tissue, such that the chemokine is effectively a pain biomarker in the TKA patient. We propose that an IL-1α-NF-κB-CCL2 signaling pathway, operating within scar-associated fibroblasts, may be therapeutically manipulated for alleviating inflammation and pain in fibrotic joints and other tissues.
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