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Introduction: Granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) is highly expressed in peripheral macrophages and microglia, and is involved in arthritis and cancer pain in animal models. However, there is limited information on GM-CSFR expression in human central nervous system (CNS), peripheral nerves, or dorsal root ganglia (DRG), particularly in chronic pain conditions.
Objectives: Immunohistochemistry was used to quantify GM-CSFR expression levels in human tissues, and functional sensory effects of GM-CSF were studied in cultured DRG neurons.
Results: Granulocyte-macrophage colony-stimulating factor receptor was markedly increased in microglia at lesional sites of multiple sclerosis spinal cords ( = 0.01), which co-localised with macrophage marker CD68 ( = 0.009). In human DRG, GM-CSFR was expressed in a subset of small/medium diameter cells (30%) and few large cells (10%), with no significant change in avulsion-injured DRG. In peripheral nerves, there was a marked decrease in axonal GM-CSFR after chronic painful nerve injury ( = 0.004) and in painful neuromas ( = 0.0043); CD-68-positive macrophages were increased ( = 0.017) but did not appear to express GM-CSFR. Although control synovium showed absent GM-CSFR immunostaining, this was markedly increased in macrophages of painful osteoarthritis knee synovium. Granulocyte-macrophage colony-stimulating factor receptor was expressed in 17 ± 1.7% of small-/medium-sized cultured adult rat DRG neurons, and in 27 ± 3.3% of TRPV1-positive neurons. Granulocyte-macrophage colony-stimulating factor treatment sensitized capsaicin responses in vitro, which were diminished by p38 MAPK or TrkA inhibitors.
Conclusion: Our findings support GM-CSFR as a therapeutic target for pain and hypersensitivity in clinical CNS and peripheral inflammatory conditions. Although GM-CSFR was decreased in chronic painful injured peripheral nerves, it could mediate CNS neuroinflammatory effects, which deserves study.
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http://dx.doi.org/10.1097/PR9.0000000000000676 | DOI Listing |
Am J Physiol Lung Cell Mol Physiol
December 2024
Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Acute exposure to ozone (O) causes upper and lower airway inflammation. We and others have previously demonstrated that O oxidizes lipids, particularly cholesterol, into electrophilic oxysterols, such as secosterol B (SecoB), which can adduct proteins, thus altering cellular signaling pathways. To investigate how O-derived oxysterols influence cytokine and chemokine release, nasal epithelial cells (HNECs) from healthy donors (N = 18 donors) were exposed to 0.
View Article and Find Full Text PDFThe proinflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) is required for host defense against a wide range of pathogens. We previously found that GM-CSF enhances inflammatory cytokine production in murine monocytes and is required for control of the intracellular bacterial pathogen . It is unclear whether GM-CSF similarly augments cytokine production in human monocytes during bacterial infection.
View Article and Find Full Text PDFDrugs Real World Outcomes
December 2024
Children's Hospital of Fudan University, 399 Wanyuan Road, Minhang District, Shanghai, China.
Background: The humanized anti-disialoganglioside-2 monoclonal antibody naxitamab was approved in the USA in 2020 for the treatment of patients with relapsed/refractory high-risk neuroblastoma, limited to the bone or bone marrow, in combination with granulocyte-macrophage colony-stimulating factor. Treatment with naxitamab under expanded access was initiated by physicians from the Children's Hospital of Fudan University, Shanghai, China, in August 2021.
Objective: We reviewed all suspected adverse reactions (ARs) reported to the Y-mAbs Argus Global Pharmacovigilance Safety Database for patients treated with naxitamab under expanded access in China from 1 August 2021 to 31 July 2022.
Int J Med Mushrooms
December 2024
Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
The traditional use of Cordyceps militaris, an entomopathogenic fungus, in East Asian medicine has been well documented. Our previous study revealed that the fruiting body powder of C. militaris, referred to as Ryukyu-kaso, contains 1,3-β-glucan and stimulates bone marrow-derived dendritic cells via a dectin-1-dependent pathway.
View Article and Find Full Text PDFBMC Infect Dis
December 2024
Division of Cardiovascular Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
Background: Cryptococcosis is an opportunistic fungal infection in immunocompromised patients. The major species include Cryptococcus grubii, Cryptococcus neoformans, and rarely, Cryptococcus gattii. Here we present a disseminated Cryptococcus gattii infection in a patient with elevated granulocyte-macrophage colony-stimulating-factor autoantibody which was successfully treated with antifungal therapy.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!