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...
Guardado en:
Autores principales: | , , , , , |
---|---|
Formato: | article |
Lenguaje: | EN |
Publicado: |
Dove Medical Press
2017
|
Materias: | |
Acceso en línea: | https://doaj.org/article/d94769321f40450ab43ecf041c2dea5a |
Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
id |
oai:doaj.org-article:d94769321f40450ab43ecf041c2dea5a |
---|---|
record_format |
dspace |
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 |
work_keys_str_mv |
AT leeyk suppressionofhumanarthritissynovialfibroblastsinflammationusingdexamethasonecarbonnanotubesviaincreasingcaveolindependentendocytosisandrecoveringmitochondrialmembranepotential AT kimsw suppressionofhumanarthritissynovialfibroblastsinflammationusingdexamethasonecarbonnanotubesviaincreasingcaveolindependentendocytosisandrecoveringmitochondrialmembranepotential AT parkjy suppressionofhumanarthritissynovialfibroblastsinflammationusingdexamethasonecarbonnanotubesviaincreasingcaveolindependentendocytosisandrecoveringmitochondrialmembranepotential AT kangwc suppressionofhumanarthritissynovialfibroblastsinflammationusingdexamethasonecarbonnanotubesviaincreasingcaveolindependentendocytosisandrecoveringmitochondrialmembranepotential AT kangyj suppressionofhumanarthritissynovialfibroblastsinflammationusingdexamethasonecarbonnanotubesviaincreasingcaveolindependentendocytosisandrecoveringmitochondrialmembranepotential AT khangd suppressionofhumanarthritissynovialfibroblastsinflammationusingdexamethasonecarbonnanotubesviaincreasingcaveolindependentendocytosisandrecoveringmitochondrialmembranepotential AT khangd suppressionofhumanarthritissynovialfibroblastsinflammationusingdexamethasonecarbonnanotubesviaincreasingcaveolindependentendocytosisandrecoveringmitochondrialmembranepotential |
_version_ |
1718396382531813376 |