Activation of NF-κB pathways mediating the inflammation and pulmonary diseases associated with atmospheric methylamine exposure. (September 2019)

• Record Type: Journal Article
• Authors: Li, Guiying; Liao, Yi; Hu, Junjie; Lu, Lirong; Zhang, Yanan; Li, Bing; An, Taicheng
• Is Part Of: Environmental pollution. Volume 252(2019):Part B
• Page Start: 1216
• Page End: 1224
• Publication Date: 2019-09
• Subjects: Methylamine -- Bronchial epithelial cell -- ROS production -- Inflammation response -- Signal pathway -- Gene expression; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2019.06.059
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: The effects of methylamine on human health have been debated for several years, but the exact adverse outcomes and definite signaling cascades have not been elucidated yet. Herein, a NF-κB signal pathway, a positive regulator of inflammation was identified as the main pathway of methylamine exposure induced adverse effects in bronchial airway cells (16HBE) for the first time. The results indicated that methylamine could stimulate the overproduction of reactive oxygen species (ROS) in cytoplasm and mitochondria of 16HBE cells. Moreover, ROS accelerate the translocation and phosphorylation of NF-κB in nucleic and promote the expression of inflammatory, such as IL-8 and IL-6. As a result, methylamine was found to be increased ROS-mediated NF-κB activation in cells, leading to the production of inflammatory cytokine. Furthermore, the results also showed that methylamine could affect the expression of cytokines related genes, p53, STAT3, Bcl2, c-myc, Cyclin D, Hes1, Mcl-1, TGF-β2. The breakdown of those cell proliferation and apoptosis related genes were leading to a common toxic mechanism of cell death. In summary, our work uncovers a mechanism by which methylamine can induce the formation of inflammation response and demonstrates potential inflammation and carcinogenesis in human airway cell upon the methylamine inhaled. Graphical abstract: Image 1 Highlights: Cell death and proliferation in epithelial cells concurred under methylamine exposure. Apoptosis and proliferation related genes were high expressed with time and dose dependent. Methylamine lead to inflammation via IL6 and IL8 overexpression in epithelial cells. Elevated ROS and activated NF-κB signaling pathway induced by methylamine exposure. Abstract : Methylamine disrupts proliferation and death homeostasis via ROS activated NF-κB pathway with inflammation and abnormal transcriptions in bronchial epithelial cell.