Journal article
Functional significance of macrophage-derived exosomes in inflammation and pain
Pain (Amsterdam), v 155(8), pp 1527-1539
Aug 2014
PMID: 24792623
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Macrophage-derived exosomes attenuated complete Freund’s adjuvant-induced thermal hyperalgesia in mice. Exosomal microRNA signature from patients with complex regional pain syndrome suggests a potential therapeutic and biomarker utility for exosomes.
Exosomes, secreted microvesicles transporting microRNAs (miRNAs), mRNAs, and proteins through bodily fluids, facilitate intercellular communication and elicit immune responses. Exosomal contents vary, depending on the source and the physiological conditions of cells, and can provide insights into how cells and systems cope with physiological perturbations. Previous analysis of circulating miRNAs in patients with complex regional pain syndrome (CRPS), a debilitating chronic pain disorder, revealed a subset of miRNAs in whole blood that are altered in the disease. To determine functional consequences of alterations in exosomal biomolecules in inflammation and pain, we investigated exosome-mediated information transfer in vitro, in a rodent model of inflammatory pain, and in exosomes from patients with CRPS. Mouse macrophage cells stimulated with lipopolysaccharides secrete exosomes containing elevated levels of cytokines and miRNAs that mediate inflammation. Transcriptome sequencing of exosomal RNA revealed global alterations in both innate and adaptive immune pathways. Exosomes from lipopolysaccharide-stimulated cells were sufficient to cause nuclear factor-κB activation in naive cells, indicating functionality in recipient cells. A single injection of exosomes attenuated thermal hyperalgesia in a murine model of inflammatory pain, suggesting an immunoprotective role for macrophage-derived exosomes. Macrophage-derived exosomes carry a protective signature that is altered when secreting cells are exposed to an inflammatory stimulus. We also show that circulating miRNAs altered in patients with complex regional pain syndrome are trafficked by exosomes. With their systemic signaling capabilities, exosomes can induce pleiotropic effects potentially mediating the multifactorial pathology underlying chronic pain, and should be explored for their therapeutic utility.
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Details
- Title
- Functional significance of macrophage-derived exosomes in inflammation and pain
- Creators
- Marguerite K McDonald - Department of Pharmacology & Physiology, Drexel University College of Medicine, Philadelphia, PA, USAYuzhen Tian - Department of Pharmacology & Physiology, Drexel University College of Medicine, Philadelphia, PA, USARehman A Qureshi - School of Biomedical Engineering, Science & Health Systems, Drexel University, Philadelphia, PA, USAMichael Gormley - Department of Cancer Biology, Thomas Jefferson University, Cancer Genomics Laboratory, Kimmel Cancer Center, Philadelphia, PA, USAAdam Ertel - Department of Cancer Biology, Thomas Jefferson University, Cancer Genomics Laboratory, Kimmel Cancer Center, Philadelphia, PA, USARuby Gao - Department of Pharmacology & Physiology, Drexel University College of Medicine, Philadelphia, PA, USAEnrique Aradillas Lopez - Department of Neurology, Drexel University College of Medicine, Philadelphia, PA, USAGuillermo M Alexander - Department of Neurology, Drexel University College of Medicine, Philadelphia, PA, USAAhmet Sacan - School of Biomedical Engineering, Science & Health Systems, Drexel University, Philadelphia, PA, USAPaolo Fortina - Department of Cancer Biology, Thomas Jefferson University, Cancer Genomics Laboratory, Kimmel Cancer Center, Philadelphia, PA, USASeena K Ajit - Department of Pharmacology & Physiology, Drexel University College of Medicine, Philadelphia, PA, USA
- Publication Details
- Pain (Amsterdam), v 155(8), pp 1527-1539
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology; School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000340309800016
- Scopus ID
- 2-s2.0-84904689513
- Other Identifier
- 991014877837004721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Anesthesiology
- Clinical Neurology
- Neurosciences