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Melatonin suppresses fibrotic responses induced by cigarette smoke via downregulation of TGF-β1

Cigarette smoke (CS) is the most important risk factor in the development of chronic obstructive pulmonary disease (COPD). Pulmonary fibrosis is an irreversible response and important feature of COPD. In this study, we investigated the effects of melatonin on fibrotic response in development of COPD...

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Autores principales: Shin, Na-Rae, Park, Ji-Won, Lee, In-Chul, Ko, Je-Won, Park, Sung-Hyeuk, Kim, Joong-Sun, Kim, Jong-Choon, Ahn, Kyung-Seop, Shin, In-Sik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707053/
https://www.ncbi.nlm.nih.gov/pubmed/29221159
http://dx.doi.org/10.18632/oncotarget.21680
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author Shin, Na-Rae
Park, Ji-Won
Lee, In-Chul
Ko, Je-Won
Park, Sung-Hyeuk
Kim, Joong-Sun
Kim, Jong-Choon
Ahn, Kyung-Seop
Shin, In-Sik
author_facet Shin, Na-Rae
Park, Ji-Won
Lee, In-Chul
Ko, Je-Won
Park, Sung-Hyeuk
Kim, Joong-Sun
Kim, Jong-Choon
Ahn, Kyung-Seop
Shin, In-Sik
author_sort Shin, Na-Rae
collection PubMed
description Cigarette smoke (CS) is the most important risk factor in the development of chronic obstructive pulmonary disease (COPD). Pulmonary fibrosis is an irreversible response and important feature of COPD. In this study, we investigated the effects of melatonin on fibrotic response in development of COPD using a CS and lipopolysaccharide (LPS) induced COPD model and cigarette smoke condensate (CSC)-stimulated NCI-H292 cells, a human mucoepidermoid cell line. Mice were exposed to CS for 1 h per day (8 cigarettes per day) from day 1 to day 7 and were treated intranasally with LPS on day 4. Melatonin (10 or 20 mg/kg) was injected intraperitoneally 1 h before CS exposure. Melatonin decreased the inflammatory cell counts in bronchoalveolar lavage fluid (BALF), with a reduction in transforming growth factor (TGF)-β1. Melatonin inhibited the expression of TGF-β1, collagen I and SMAD3 phosphorylation in lung tissue exposed to CS and LPS. In CSC-stimulated H292 cells, melatonin suppressed the elevated expression of fibrotic mediators induced by CSC treatment. Melatonin reduced the expression of TGF-β1, collagen I, SMAD3 and p38 phosphorylation in CSC-stimulated H292 cells. In addition, cotreatment with melatonin and TGF-β1 inhibitors significantly limited fibrotic mediators, with greater reductions in the expression of TGF-β1, collagen I, SMAD3 and p38 phosphorylation than those of H292 cells treated with TGF-β1 inhibitor alone. Taken together, melatonin effectively inhibited fibrotic responses induced by CS and LPS exposure, which was related to the downregulation of TGF-β1. Therefore, our results suggest that melatonin may suppress the pulmonary fibrotic response induced by CS.
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spelling pubmed-57070532017-12-07 Melatonin suppresses fibrotic responses induced by cigarette smoke via downregulation of TGF-β1 Shin, Na-Rae Park, Ji-Won Lee, In-Chul Ko, Je-Won Park, Sung-Hyeuk Kim, Joong-Sun Kim, Jong-Choon Ahn, Kyung-Seop Shin, In-Sik Oncotarget Research Paper Cigarette smoke (CS) is the most important risk factor in the development of chronic obstructive pulmonary disease (COPD). Pulmonary fibrosis is an irreversible response and important feature of COPD. In this study, we investigated the effects of melatonin on fibrotic response in development of COPD using a CS and lipopolysaccharide (LPS) induced COPD model and cigarette smoke condensate (CSC)-stimulated NCI-H292 cells, a human mucoepidermoid cell line. Mice were exposed to CS for 1 h per day (8 cigarettes per day) from day 1 to day 7 and were treated intranasally with LPS on day 4. Melatonin (10 or 20 mg/kg) was injected intraperitoneally 1 h before CS exposure. Melatonin decreased the inflammatory cell counts in bronchoalveolar lavage fluid (BALF), with a reduction in transforming growth factor (TGF)-β1. Melatonin inhibited the expression of TGF-β1, collagen I and SMAD3 phosphorylation in lung tissue exposed to CS and LPS. In CSC-stimulated H292 cells, melatonin suppressed the elevated expression of fibrotic mediators induced by CSC treatment. Melatonin reduced the expression of TGF-β1, collagen I, SMAD3 and p38 phosphorylation in CSC-stimulated H292 cells. In addition, cotreatment with melatonin and TGF-β1 inhibitors significantly limited fibrotic mediators, with greater reductions in the expression of TGF-β1, collagen I, SMAD3 and p38 phosphorylation than those of H292 cells treated with TGF-β1 inhibitor alone. Taken together, melatonin effectively inhibited fibrotic responses induced by CS and LPS exposure, which was related to the downregulation of TGF-β1. Therefore, our results suggest that melatonin may suppress the pulmonary fibrotic response induced by CS. Impact Journals LLC 2017-10-09 /pmc/articles/PMC5707053/ /pubmed/29221159 http://dx.doi.org/10.18632/oncotarget.21680 Text en Copyright: © 2017 Shin et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Shin, Na-Rae
Park, Ji-Won
Lee, In-Chul
Ko, Je-Won
Park, Sung-Hyeuk
Kim, Joong-Sun
Kim, Jong-Choon
Ahn, Kyung-Seop
Shin, In-Sik
Melatonin suppresses fibrotic responses induced by cigarette smoke via downregulation of TGF-β1
title Melatonin suppresses fibrotic responses induced by cigarette smoke via downregulation of TGF-β1
title_full Melatonin suppresses fibrotic responses induced by cigarette smoke via downregulation of TGF-β1
title_fullStr Melatonin suppresses fibrotic responses induced by cigarette smoke via downregulation of TGF-β1
title_full_unstemmed Melatonin suppresses fibrotic responses induced by cigarette smoke via downregulation of TGF-β1
title_short Melatonin suppresses fibrotic responses induced by cigarette smoke via downregulation of TGF-β1
title_sort melatonin suppresses fibrotic responses induced by cigarette smoke via downregulation of tgf-β1
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707053/
https://www.ncbi.nlm.nih.gov/pubmed/29221159
http://dx.doi.org/10.18632/oncotarget.21680
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