Topical Administration of Melatonin-Loaded Extracellular Vesicle-Mimetic Nanovesicles Improves 2,4-Dinitrofluorobenzene-Induced Atopic Dermatitis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. Generation of Melatonin-Loaded Extracellular Vesicle-Mimetic NVs
2.3. Cryo-Electron Microscopy and Nanoparticle Tracking Analysis
2.4. Western Blotting
2.5. Quantification of Melatonin in Extracellular Vesicle-Mimetic NVs
2.6. In Vitro β-Hexosaminidase Release Assay
2.7. Animal Care
2.8. Atopic Dermatitis-Like Mouse Model
2.9. Enzyme-Linked Immunosorbent Assay (ELISA)
2.10. Histological Analysis
2.11. Statistical Analysis
3. Results
3.1. Generation and Characterization of NVs and Melatonin-Loaded NVs
3.2. In Vitro Anti-Inflammatory Effect of MelaNVs in RAW264.7 and RBL-2H3 Cells
3.3. MelaNVs Ameliorate DNCB-Induced AD and Suppress Mast Cell Infiltration and Fibrosis in AD-like Skin Lesions
3.4. MelaNVs Decrease Serum IgE Levels, Restore Th1/Th2 Cytokine Balance, and Suppress the Release of Inflammatory Cytokines in AD-like Skin Lesions
4. Discussion
- The anti-inflammatory effects of MelaNVs in LPS-stimulated RAW264.7 cells and C48/80-stimulated RBL-2H3 cells.
- We demonstrated that MelaNVs could improve AD-like symptoms and suppress mast cell infiltration and fibrosis in AD-like skin lesions. MelaNVs decreased serum IgE, restored IFN-γ and IL-4 levels, and inhibited COX-2, TNF-α, and PAR-2 expression.
- These results suggest that MelaNVs have an excellent anti-atopic effect and can be used for the treatment of AD.
- As MelaNVs are an excellent melatonin delivery system, MelaNVs may also be used in other skin disease models, including decubitus and eye disease, to deliver melatonin.
Author Contributions
Funding
Institutional Review Board Statement
Conflicts of Interest
References
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Kim, Y.S.; Go, G.; Yun, C.-W.; Yea, J.-H.; Yoon, S.; Han, S.-Y.; Lee, G.; Lee, M.-Y.; Lee, S.H. Topical Administration of Melatonin-Loaded Extracellular Vesicle-Mimetic Nanovesicles Improves 2,4-Dinitrofluorobenzene-Induced Atopic Dermatitis. Biomolecules 2021, 11, 1450. https://doi.org/10.3390/biom11101450
Kim YS, Go G, Yun C-W, Yea J-H, Yoon S, Han S-Y, Lee G, Lee M-Y, Lee SH. Topical Administration of Melatonin-Loaded Extracellular Vesicle-Mimetic Nanovesicles Improves 2,4-Dinitrofluorobenzene-Induced Atopic Dermatitis. Biomolecules. 2021; 11(10):1450. https://doi.org/10.3390/biom11101450
Chicago/Turabian StyleKim, Yoon Seon, Gyeongyun Go, Chul-Won Yun, Ji-Hye Yea, Sungtae Yoon, Su-Yeon Han, Gaeun Lee, Mi-Young Lee, and Sang Hun Lee. 2021. "Topical Administration of Melatonin-Loaded Extracellular Vesicle-Mimetic Nanovesicles Improves 2,4-Dinitrofluorobenzene-Induced Atopic Dermatitis" Biomolecules 11, no. 10: 1450. https://doi.org/10.3390/biom11101450