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Suppression of human arthritis synovial fibroblasts inflammation using dexamethasone-carbon nanotubes via increasing caveolin-dependent endocytosis and recovering mitochondrial membrane potential
Dexamethasone (DEX), a non-particulate glucocorticoid (GC) to inhibit anti-inflammatory response, has been widely used for the treatment of various diseases such as arthritis, cancer, asthma, chronic obstructive pulmonary disease, cerebral edema, and multiple sclerosis. However, prolonged and/or hig...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove Medical Press
2017
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5557625/ https://www.ncbi.nlm.nih.gov/pubmed/28848352 http://dx.doi.org/10.2147/IJN.S142122 |
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author | Lee, Yeon Kyung Kim, Sang-Woo Park, Jun-Young Kang, Woong Chol Kang, Youn Joo Khang, Dongwoo |
author_facet | Lee, Yeon Kyung Kim, Sang-Woo Park, Jun-Young Kang, Woong Chol Kang, Youn Joo Khang, Dongwoo |
author_sort | Lee, Yeon Kyung |
collection | PubMed |
description | Dexamethasone (DEX), a non-particulate glucocorticoid (GC) to inhibit anti-inflammatory response, has been widely used for the treatment of various diseases such as arthritis, cancer, asthma, chronic obstructive pulmonary disease, cerebral edema, and multiple sclerosis. However, prolonged and/or high-dose GC therapy can cause various serious adverse effects (adrenal insufficiency, hyperglycemia, Cushing’s syndrome, osteoporosis, Charcot arthropathy, etc). In this study, developed DEX-carbon nanotube (CNT) conjugates improved intracellular drug delivery via increased caveolin-dependent endocytosis and ultimately suppressed the expression of major pro-inflammatory cytokines in tumor necrosis factor-α (TNF-α)-stimulated human fibroblast-like synoviocytes (FLS) at low drug concentrations. Specifically, DEX on polyethylene-glycol (PEG)-coated CNTs induced caveolin uptake, recovered mitochondrial disruption, and inhibited reactive oxygen species production by targeting mitochondria that was released from the early endosome in TNF-α-stimulated FLS. The obtained results clearly demonstrated that DEX-PEG-coated CNTs significantly inhibited the inflammation by FLS in rheumatoid arthritis (RA) by achieving greater drug uptake and efficient intracellular drug release from the endosome, thus suggesting a mechanism of effective low-dose GC therapy to treat inflammatory diseases, including RA and osteoarthritis. |
format | Online Article Text |
id | pubmed-5557625 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-55576252017-08-28 Suppression of human arthritis synovial fibroblasts inflammation using dexamethasone-carbon nanotubes via increasing caveolin-dependent endocytosis and recovering mitochondrial membrane potential Lee, Yeon Kyung Kim, Sang-Woo Park, Jun-Young Kang, Woong Chol Kang, Youn Joo Khang, Dongwoo Int J Nanomedicine Original Research Dexamethasone (DEX), a non-particulate glucocorticoid (GC) to inhibit anti-inflammatory response, has been widely used for the treatment of various diseases such as arthritis, cancer, asthma, chronic obstructive pulmonary disease, cerebral edema, and multiple sclerosis. However, prolonged and/or high-dose GC therapy can cause various serious adverse effects (adrenal insufficiency, hyperglycemia, Cushing’s syndrome, osteoporosis, Charcot arthropathy, etc). In this study, developed DEX-carbon nanotube (CNT) conjugates improved intracellular drug delivery via increased caveolin-dependent endocytosis and ultimately suppressed the expression of major pro-inflammatory cytokines in tumor necrosis factor-α (TNF-α)-stimulated human fibroblast-like synoviocytes (FLS) at low drug concentrations. Specifically, DEX on polyethylene-glycol (PEG)-coated CNTs induced caveolin uptake, recovered mitochondrial disruption, and inhibited reactive oxygen species production by targeting mitochondria that was released from the early endosome in TNF-α-stimulated FLS. The obtained results clearly demonstrated that DEX-PEG-coated CNTs significantly inhibited the inflammation by FLS in rheumatoid arthritis (RA) by achieving greater drug uptake and efficient intracellular drug release from the endosome, thus suggesting a mechanism of effective low-dose GC therapy to treat inflammatory diseases, including RA and osteoarthritis. Dove Medical Press 2017-08-10 /pmc/articles/PMC5557625/ /pubmed/28848352 http://dx.doi.org/10.2147/IJN.S142122 Text en © 2017 Lee et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Lee, Yeon Kyung Kim, Sang-Woo Park, Jun-Young Kang, Woong Chol Kang, Youn Joo Khang, Dongwoo Suppression of human arthritis synovial fibroblasts inflammation using dexamethasone-carbon nanotubes via increasing caveolin-dependent endocytosis and recovering mitochondrial membrane potential |
title | Suppression of human arthritis synovial fibroblasts inflammation using dexamethasone-carbon nanotubes via increasing caveolin-dependent endocytosis and recovering mitochondrial membrane potential |
title_full | Suppression of human arthritis synovial fibroblasts inflammation using dexamethasone-carbon nanotubes via increasing caveolin-dependent endocytosis and recovering mitochondrial membrane potential |
title_fullStr | Suppression of human arthritis synovial fibroblasts inflammation using dexamethasone-carbon nanotubes via increasing caveolin-dependent endocytosis and recovering mitochondrial membrane potential |
title_full_unstemmed | Suppression of human arthritis synovial fibroblasts inflammation using dexamethasone-carbon nanotubes via increasing caveolin-dependent endocytosis and recovering mitochondrial membrane potential |
title_short | Suppression of human arthritis synovial fibroblasts inflammation using dexamethasone-carbon nanotubes via increasing caveolin-dependent endocytosis and recovering mitochondrial membrane potential |
title_sort | suppression of human arthritis synovial fibroblasts inflammation using dexamethasone-carbon nanotubes via increasing caveolin-dependent endocytosis and recovering mitochondrial membrane potential |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5557625/ https://www.ncbi.nlm.nih.gov/pubmed/28848352 http://dx.doi.org/10.2147/IJN.S142122 |
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