Melatonin attenuates neutrophil inflammation and mucus secretion in cigarette smoke‐induced chronic obstructive pulmonary diseases via the suppression of Erk‐Sp1 signaling

Abstract

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.

Cigarette smoke extract-induced p120-mediated NF-κB activation in human epithelial cells is dependent on the RhoA/ROCK pathway

“…Cigarette smoke exposure activates NF-κB signaling and leads to lung inflammation, but its underlying molecular mechanism remains poorly understood. Erk1/2 is involved in regulating NF-κB signaling in mice lungs that are exposed to cigarette smoke2630. In addition, the RAGE-Ras–NF-kB axis has been reported to likely be associated with several smoking-related inflammatory lung diseases3132.…”

Cytosolic Phospholipase A2α Promotes Pulmonary Inflammation and Systemic Disease during Streptococcus pneumoniae Infection

“…Human mucoepidermoid pulmonary carcinoma cell line NCI-H292 (H292) has been used in a number of studies of pulmonary inflammation and/or eicosanoid production (88)(89)(90)(91)(92), as well as in studies of pulmonary infection by bacteria (93)(94)(95). These cells were cultured in RPMI 1640 medium (American Type Culture Collection, Manassas, VA) supplemented with 10% fetal bovine serum, 2 mM L-glutamine, and penicillin-streptomycin.…”

Melatonin reverses the enhanced oxidative damage to membrane lipids and improves skin biophysical characteristics in former-smokers – A study in postmenopausal women

“…These findings are in agreement with the assumption that melatonin does not affect processes at the physiological level. Such an assumption has been repeatedly confirmed in experimental and clinical studies in which melatonin used separately did not change the level of oxidative damage to macromolecules but, at the same time, it revealed protective effects against prooxidative agents [3,4,8,[28][29][30][31][32].…”

“…Concerning the protective influence of melatonin on deleterious effects caused by smoking, there are some studies published which concern this protective influence, but they relate to current smoking [32,34]. The presented study is the first to document protective effects of melatonin against oxidative damage to macromolecules in formersmokers.…”