Suppression of human arthritis synovial fibroblasts inflammation using dexamethasone-carbon nanotubes via increasing caveolin-dependent endocytosis and recovering mitochondrial membrane potential

Yeon Kyung Lee,1,* Sang-Woo Kim,1,* Jun-Young Park,1 Woong Chol Kang,2 Youn Joo Kang,3 Dongwoo Khang1,4 1Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 2Department of Cardiology, Gil Medical Center, Gachon University, Incheon, 3Department of Rehabilitation Medicine, Eulji Hospital, Eu...

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Autores principales: Lee YK, Kim SW, Park JY, Kang WC, Kang YJ, Khang D
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Publicado: Dove Medical Press 2017
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spelling oai:doaj.org-article:d94769321f40450ab43ecf041c2dea5a2021-12-02T11:01:34ZSuppression of human arthritis synovial fibroblasts inflammation using dexamethasone-carbon nanotubes via increasing caveolin-dependent endocytosis and recovering mitochondrial membrane potential1178-2013https://doaj.org/article/d94769321f40450ab43ecf041c2dea5a2017-08-01T00:00:00Zhttps://www.dovepress.com/suppression-of-human-arthritis-synovial-fibroblasts-inflammation-using-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yeon Kyung Lee,1,* Sang-Woo Kim,1,* Jun-Young Park,1 Woong Chol Kang,2 Youn Joo Kang,3 Dongwoo Khang1,4 1Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 2Department of Cardiology, Gil Medical Center, Gachon University, Incheon, 3Department of Rehabilitation Medicine, Eulji Hospital, Eulji University School of Medicine, Seoul, 4Department of Physiology, College of Medicine, Gachon University, Incheon, South Korea *These authors contributed equally to this work Abstract: 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. Keywords: carbon nanotubes, polyethylene-glycol, dexamethasone, arthritis, fibroblast-like synoviocytes, caveolin-dependent endocytosis Lee YKKim SWPark JYKang WCKang YJKhang DKhang DDove Medical PressarticleCarbon nanotubesPolyethylene-glycolDexamethasoneArthritisFibroblast-like synoviocytesCaveolin-dependent endocytosisMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 5761-5779 (2017)
institution DOAJ
collection DOAJ
language EN
topic Carbon nanotubes
Polyethylene-glycol
Dexamethasone
Arthritis
Fibroblast-like synoviocytes
Caveolin-dependent endocytosis
Medicine (General)
R5-920
spellingShingle Carbon nanotubes
Polyethylene-glycol
Dexamethasone
Arthritis
Fibroblast-like synoviocytes
Caveolin-dependent endocytosis
Medicine (General)
R5-920
Lee YK
Kim SW
Park JY
Kang WC
Kang YJ
Khang D
Khang D
Suppression of human arthritis synovial fibroblasts inflammation using dexamethasone-carbon nanotubes via increasing caveolin-dependent endocytosis and recovering mitochondrial membrane potential
description Yeon Kyung Lee,1,* Sang-Woo Kim,1,* Jun-Young Park,1 Woong Chol Kang,2 Youn Joo Kang,3 Dongwoo Khang1,4 1Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 2Department of Cardiology, Gil Medical Center, Gachon University, Incheon, 3Department of Rehabilitation Medicine, Eulji Hospital, Eulji University School of Medicine, Seoul, 4Department of Physiology, College of Medicine, Gachon University, Incheon, South Korea *These authors contributed equally to this work Abstract: 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. Keywords: carbon nanotubes, polyethylene-glycol, dexamethasone, arthritis, fibroblast-like synoviocytes, caveolin-dependent endocytosis 
format article
author Lee YK
Kim SW
Park JY
Kang WC
Kang YJ
Khang D
Khang D
author_facet Lee YK
Kim SW
Park JY
Kang WC
Kang YJ
Khang D
Khang D
author_sort Lee YK
title 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_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_sort suppression of human arthritis synovial fibroblasts inflammation using dexamethasone-carbon nanotubes via increasing caveolin-dependent endocytosis and recovering mitochondrial membrane potential
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/d94769321f40450ab43ecf041c2dea5a
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