Abstract
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.
Highlights
The prevalence and mortality associated with chronic obstructive pulmonary disease (COPD) continues to increase worldwide
We investigated the potential of melatonin as a PDE4 inhibitor in the treatment of COPD by exposing mice to Cigarette smoke (CS) and stimulating airway epithelial cells by cigarette smoke condensate (CSC)
Melatonin is used for the treatment of various diseases due to its pharmacological properties [17,18]
Summary
The prevalence and mortality associated with chronic obstructive pulmonary disease (COPD) continues to increase worldwide. It is regarded as an important disease threatening human health [1]. Cigarette smoke (CS) is regarded as a crucial cause for the development of COPD, and it generates various stimuli, such as proinflammatory mediators and oxidative stress, resulting in pulmonary inflammation [3]. Continuous smoking increases the incidence of COPD via the elevation of inflammatory responses and oxidative damage. Inhibition of the inflammation and oxidative damage induced by CS is considered an important strategy for the effective control of COPD [4]
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