Aeroallergens Induce Reactive Oxygen Species Production and DNA Damage and Dampen Antioxidant Responses in Bronchial Epithelial Cells

• Published in: The Journal of immunology (1950) Vol. 199; no. 1; pp. 39 - 47
• Main Authors: Chan, Tze Khee, Tan, W S Daniel, Peh, Hong Yong, Wong, W S Fred
• Format: Journal Article
• Language: English
• Published: United States American Association of Immunologists 01-07-2017
• Subjects: Acetophenones - immunology; Acetophenones - pharmacology; Air; Allergens; Allergens - immunology; Animals; Antioxidants; Antioxidants - pharmacology; Antioxidants - physiology; Apoptosis - drug effects; Apoptosis Inducing Factor - genetics; Apoptosis Inducing Factor - metabolism; Asthma; Asthma - etiology; Asthma - immunology; Asthma - physiopathology; Bronchi - cytology; Bronchi - immunology; Bronchi - metabolism; Catalase; Catalase - metabolism; Cell death; Cell proliferation; Cell Proliferation - drug effects; Cellular manufacture; Cytotoxicity; Damage prevention; Deoxyribonucleic acid; DNA; DNA Damage; Epithelial cells; Epithelial Cells - immunology; Epithelial Cells - metabolism; Epithelium; Exposure; Glutathione; Glutathione - pharmacology; House dust; Humans; Inhibitors; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Mitochondria; NAD(P)H oxidase; NADPH Oxidase 2; NADPH Oxidase 4; NADPH Oxidases - genetics; NADPH Oxidases - metabolism; Nitrogen; Oxidative stress; Proteolysis; Pyroglyphidae - immunology; Reactive nitrogen species; Reactive oxygen species; Reactive Oxygen Species - metabolism; Respiratory tract diseases; Risk factors
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1600657

Exposure to environmental allergens is a major risk factor for asthma development. Allergens possess proteolytic activity that is capable of disrupting the airway epithelium. Although there is increasing evidence pointing to asthma as an epithelial disease, the underlying mechanism that drives asthma has not been fully elucidated. In this study, we investigated the direct DNA damage potential of aeroallergens on human bronchial epithelial cells and elucidated the mechanisms mediating the damage. Human bronchial epithelial cells, BEAS-2B, directly exposed to house dust mites (HDM) resulted in enhanced DNA damage, as measured by the CometChip and the staining of DNA double-strand break marker, γH2AX. HDM stimulated cellular reactive oxygen species production, increased mitochondrial oxidative stress, and promoted nitrosative stress. Notably, expression of nuclear factor erythroid 2-related factor 2-dependent antioxidant genes was reduced immediately after HDM exposure, suggesting that HDM altered antioxidant responses. HDM exposure also reduced cell proliferation and induced cell death. Importantly, HDM-induced DNA damage can be prevented by the antioxidants glutathione and catalase, suggesting that HDM-induced reactive oxygen and nitrogen species can be neutralized by antioxidants. Mechanistic studies revealed that HDM-induced cellular injury is NADPH oxidase (NOX)-dependent, and apocynin, a NOX inhibitor, protected cells from double-strand breaks induced by HDM. Our results show that direct exposure of bronchial epithelial cells to HDM leads to the production of reactive oxygen and nitrogen species that damage DNA and induce cytotoxicity. Antioxidants and NOX inhibitors can prevent HDM-induced DNA damage, revealing a novel role for antioxidants and NOX inhibitors in mitigating allergic airway disease.