Del-1 Plays a Protective Role against COPD Development by Inhibiting Inflammation and Apoptosis.
Nakwon KwakKyoung-Hee LeeJisu WooJiyeon KimJimyung ParkChang-Hoon LeeChul-Gyu YooPublished in: International journal of molecular sciences (2024)
Neutrophilic inflammation is a prominent feature of chronic obstructive pulmonary disease (COPD). Developmental endothelial locus-1 (Del-1) has been reported to limit excessive neutrophilic inflammation by inhibiting neutrophil adhesion to the vascular endothelial cells. However, the effects of Del-1 in COPD are not known. We investigated the role of Del-1 in the pathogenesis of COPD. Del-1 protein expression was decreased in the lungs of COPD patients, especially in epithelial cells and alveolar macrophages. In contrast to human lung tissue, Del-1 expression was upregulated in lung tissue from mice treated with cigarette smoke extracts (CSE). Overexpression of Del-1 significantly suppressed IL-8 release and apoptosis in CSE-treated epithelial cells. In contrast, knockdown of Del-1 enhanced IL-8 release and apoptosis. In macrophages, overexpression of Del-1 significantly suppressed inflammatory cytokine release, and knockdown of Del-1 enhanced it. This anti-inflammatory effect was mediated by inhibiting the phosphorylation and acetylation of NF-κB p65. Nuclear factor erythroid 2-related factor 2 (Nrf2) activators, such as quercetin, resveratrol, and sulforaphane, increased Del-1 in both cell types. These results suggest that Del-1, mediated by Nrf2, plays a protective role against the pathogenesis of COPD, at least in part through anti-inflammatory and anti-apoptotic effects.
Keyphrases
- oxidative stress
- chronic obstructive pulmonary disease
- lung function
- endothelial cells
- nuclear factor
- cell death
- signaling pathway
- anti inflammatory
- magnetic resonance
- magnetic resonance imaging
- endoplasmic reticulum stress
- mesenchymal stem cells
- toll like receptor
- stem cells
- cell cycle arrest
- computed tomography
- end stage renal disease
- newly diagnosed
- long non coding rna
- cystic fibrosis
- high resolution
- candida albicans
- pi k akt
- protein kinase
- vascular endothelial growth factor
- pseudomonas aeruginosa
- physical activity
- biofilm formation
- contrast enhanced
- weight gain
- cell migration
- atomic force microscopy