Keratinocyte-derived microvesicle particles mediate Ultraviolet B radiation induced systemic immunosuppression
| Autor: | Jinju Wang, Benita Y. Wu, Cameron L McGlone, Langni Liu, Ji C. Bihl, Azeezat A. Awoyemi, R Michael Johnson, Benjamin Schmeusser, Christina Knisely, Katherine E. Fahy, Elizabeth Cates, Craig A Rohan, Pariksha Thapa, Christina Borchers, David R. Cool, Lisa E. Kelly, Yanfang Chen, Jeffrey B. Travers, Ravi P. Sahu, Michael G. Kemp, Christine M. Rapp, Amy R. Williams, Zafer Sattouf |
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| Rok vydání: | 2021 |
| Předmět: |
Keratinocytes
0301 basic medicine Ultraviolet Rays Platelet Membrane Glycoproteins Cell Line Receptors G-Protein-Coupled Mice 03 medical and health sciences 0302 clinical medicine Cell-Derived Microparticles Immune Tolerance medicine Animals Humans Platelet Activating Factor skin and connective tissue diseases Receptor Carcinogen Mice Knockout integumentary system Chemistry Microvesicle General Medicine Lipid signaling medicine.disease Sphingomyelin Phosphodiesterase 030104 developmental biology medicine.anatomical_structure Photobiology 030220 oncology & carcinogenesis Cancer research Female Skin cancer Acid sphingomyelinase Keratinocyte Research Article medicine.drug |
| Zdroj: | J Clin Invest |
| ISSN: | 1558-8238 |
| DOI: | 10.1172/jci144963 |
| Popis: | A complete carcinogen, ultraviolet B (UVB) radiation (290-320 nm), is the major cause of skin cancer. UVB-induced systemic immunosuppression that contributes to photocarcinogenesis is due to the glycerophosphocholine-derived lipid mediator platelet-activating factor (PAF). A major question in photobiology is how UVB radiation, which only absorbs appreciably in the epidermal layers of skin, can generate systemic effects. UVB exposure and PAF receptor (PAFR) activation in keratinocytes induce the release of large numbers of microvesicle particles (MVPs; extracellular vesicles ranging from 100 to 1000 nm in size). MVPs released from skin keratinocytes in vitro in response to UVB (UVB-MVPs) are dependent on the keratinocyte PAFR. Here, we used both pharmacologic and genetic approaches in cells and mice to show that both the PAFR and enzyme acid sphingomyelinase (aSMase) were necessary for UVB-MVP generation. Our discovery that the calcium-sensing receptor is a keratinocyte-selective MVP marker allowed us to determine that UVB-MVPs leaving the keratinocyte can be found systemically in mice and humans following UVB exposure. Moreover, we found that UVB-MVPs contained bioactive contents including PAFR agonists that allowed them to serve as effectors for UVB downstream effects, in particular UVB-mediated systemic immunosuppression. |
| Databáze: | OpenAIRE |
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