Melatonin attenuates neutrophil inflammation and mucus secretion in cigarette smoke-induced chronic obstructive pulmonary diseases via the suppression of Erk-Sp1 signaling
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- Melatonin attenuates neutrophil inflammation and mucus secretion in cigarette smoke-induced chronic obstructive pulmonary diseases via the suppression of Erk-Sp1 signaling
- In Sik Shin; Na Rae Shin; Ji Won Park; Chan Mi Jeon; Ju Mi Hong; Ok-Kyoung Kwon; J S Kim; In Chul Lee; J C Kim; Sei-Ryang Oh; Kyung Seop Ahn
- Bibliographic Citation
- Journal of Pineal Research, vol. 58, no. 1, pp. 50-60
- Publication Year
- The incidence of chronic obstructive pulmonary disease (COPD) has substantially increased in recent decade. Cigarette smoke (CS) is the most important risk factor in the development of COPD. In this study, we investigated the effects of melatonin on the development of COPD using a CS and lipopolysaccharide (LPS)-induced COPD model and cigarette smoke condensate (CSC)-stimulated NCI-H292 cells, a human mucoepidermoid carcinoma cell. On day 4, the mice were treated intranasally with LPS. The mice were exposed to CS for 1 hr per day (8 cigarettes per day) from day 1 to day 7. Melatonin (10 or 20 mg/kg) was injected intraperitoneally 1 hr before CS exposure. Melatonin markedly decreased the neutrophil count in the BALF, with reduction in the proinflammatory mediators and MUC5AC. Melatonin inhibited Erk phosphorylation and Sp1 expression induced by CS and LPS treatment. Additionally, melatonin decreased airway inflammation with a reduction in myeloperoxidase expression in lung tissue. In in vitro experiments, melatonin suppressed the elevated expression of proinflammatory mediators induced by CSC treatment. Melatonin reduced Erk phosphorylation and Sp1 expression in CSC-stimulated H292 cells. In addition, cotreatment of melatonin and Erk inhibitors significantly limited the proinflammatory mediators with greater reductions in Erk phosphorylation and Sp1 expression than that observed in H292 cells treated with Erk inhibitor alone. Taken together, melatonin effectively inhibited the neutrophil airway inflammation induced by CS and LPS treatment, which was closely related to downregulation of Erk phosphorylation. These findings suggest that melatonin has a therapeutic potential for the treatment of COPD.
- chronic obstructive pulmonary diseasecigarette smokeErk/Sp1Melatonin
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- Ochang Branch Institute > Division of National Bio-Infrastructure > Bio-Resource Central Bank > 1. Journal Articles
Jeonbuk Branch Institute > Functional Biomaterial Research Center > 1. Journal Articles
Ochang Branch Institute > 1. Journal Articles
Ochang Branch Institute > Natural Product Research Center > 1. Journal Articles
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