The Involvement of PDE4 in the Protective Effects of Melatonin on Cigarette-Smoke-Induced Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a significant disease threatening human health. Currently, roflumilast, a phosphodiesterase (PDE)4 inhibitor, is recommended as a therapeutic agent for COPD. In this study, we investigated the therapeutic effects of melatonin against COPD, focusing on...

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Autores principales:	Je-Oh Lim, Woong-Il Kim, Se-Jin Lee, So-Won Pak, Young-Kwon Cho, Jong-Choon Kim, Joong-Sun Kim, In-Sik Shin
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	melatonin chronic obstructive pulmonary disease cigarette smoke phosphodiesterase 4 MMP-9 Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/be80934177a8409d9fa158d331610697
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spelling	oai:doaj.org-article:be80934177a8409d9fa158d3316106972021-11-11T18:34:06ZThe Involvement of PDE4 in the Protective Effects of Melatonin on Cigarette-Smoke-Induced Chronic Obstructive Pulmonary Disease10.3390/molecules262165881420-3049https://doaj.org/article/be80934177a8409d9fa158d3316106972021-10-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6588https://doaj.org/toc/1420-3049Chronic obstructive pulmonary disease (COPD) is a significant disease threatening human health. Currently, roflumilast, a phosphodiesterase (PDE)4 inhibitor, is recommended as a therapeutic agent for COPD. In this study, we investigated the therapeutic effects of melatonin against COPD, focusing on determining whether it is a PDE4 inhibitor via in vivo and in vitro experiment using cigarette smoke (CS) and cigarette smoke condensate (CSC), respectively. In the in vivo experiments, melatonin treatment reduced inflammatory responses, including inflammatory cell counts. Melatonin treatment also suppressed the CS-exposure-induced upregulation of cytokine and matrix metalloproteinase (MMP)-9, reduced the PDE4B expression, and elevated cAMP levels. In addition, these effects were synergistic, as melatonin and roflumilast cotreatment eventually ameliorated the CS-exposure-induced worsening of lung function. In the CSC-stimulated NCI-H292 cells, melatonin inhibited elevation in the levels of inflammatory cytokines, MMP-9, and PDE4, and elevated cAMP levels. Furthermore, melatonin and roflumilast cotreatment was more effective on inflammatory responses than only melatonin or roflumilast treatment. Our results indicate that melatonin relieves inflammatory response and loss of lung function in COPD, which is associated with decreased PDE4 expression. Therefore, we suggest that melatonin is a putative candidate for the treatment of COPD.Je-Oh LimWoong-Il KimSe-Jin LeeSo-Won PakYoung-Kwon ChoJong-Choon KimJoong-Sun KimIn-Sik ShinMDPI AGarticlemelatoninchronic obstructive pulmonary diseasecigarette smokephosphodiesterase 4MMP-9Organic chemistryQD241-441ENMolecules, Vol 26, Iss 6588, p 6588 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	melatonin chronic obstructive pulmonary disease cigarette smoke phosphodiesterase 4 MMP-9 Organic chemistry QD241-441
spellingShingle	melatonin chronic obstructive pulmonary disease cigarette smoke phosphodiesterase 4 MMP-9 Organic chemistry QD241-441 Je-Oh Lim Woong-Il Kim Se-Jin Lee So-Won Pak Young-Kwon Cho Jong-Choon Kim Joong-Sun Kim In-Sik Shin The Involvement of PDE4 in the Protective Effects of Melatonin on Cigarette-Smoke-Induced Chronic Obstructive Pulmonary Disease
description	Chronic obstructive pulmonary disease (COPD) is a significant disease threatening human health. Currently, roflumilast, a phosphodiesterase (PDE)4 inhibitor, is recommended as a therapeutic agent for COPD. In this study, we investigated the therapeutic effects of melatonin against COPD, focusing on determining whether it is a PDE4 inhibitor via in vivo and in vitro experiment using cigarette smoke (CS) and cigarette smoke condensate (CSC), respectively. In the in vivo experiments, melatonin treatment reduced inflammatory responses, including inflammatory cell counts. Melatonin treatment also suppressed the CS-exposure-induced upregulation of cytokine and matrix metalloproteinase (MMP)-9, reduced the PDE4B expression, and elevated cAMP levels. In addition, these effects were synergistic, as melatonin and roflumilast cotreatment eventually ameliorated the CS-exposure-induced worsening of lung function. In the CSC-stimulated NCI-H292 cells, melatonin inhibited elevation in the levels of inflammatory cytokines, MMP-9, and PDE4, and elevated cAMP levels. Furthermore, melatonin and roflumilast cotreatment was more effective on inflammatory responses than only melatonin or roflumilast treatment. Our results indicate that melatonin relieves inflammatory response and loss of lung function in COPD, which is associated with decreased PDE4 expression. Therefore, we suggest that melatonin is a putative candidate for the treatment of COPD.
format	article
author	Je-Oh Lim Woong-Il Kim Se-Jin Lee So-Won Pak Young-Kwon Cho Jong-Choon Kim Joong-Sun Kim In-Sik Shin
author_facet	Je-Oh Lim Woong-Il Kim Se-Jin Lee So-Won Pak Young-Kwon Cho Jong-Choon Kim Joong-Sun Kim In-Sik Shin
author_sort	Je-Oh Lim
title	The Involvement of PDE4 in the Protective Effects of Melatonin on Cigarette-Smoke-Induced Chronic Obstructive Pulmonary Disease
title_short	The Involvement of PDE4 in the Protective Effects of Melatonin on Cigarette-Smoke-Induced Chronic Obstructive Pulmonary Disease
title_full	The Involvement of PDE4 in the Protective Effects of Melatonin on Cigarette-Smoke-Induced Chronic Obstructive Pulmonary Disease
title_fullStr	The Involvement of PDE4 in the Protective Effects of Melatonin on Cigarette-Smoke-Induced Chronic Obstructive Pulmonary Disease
title_full_unstemmed	The Involvement of PDE4 in the Protective Effects of Melatonin on Cigarette-Smoke-Induced Chronic Obstructive Pulmonary Disease
title_sort	involvement of pde4 in the protective effects of melatonin on cigarette-smoke-induced chronic obstructive pulmonary disease
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/be80934177a8409d9fa158d331610697
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The Involvement of PDE4 in the Protective Effects of Melatonin on Cigarette-Smoke-Induced Chronic Obstructive Pulmonary Disease

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