Polyhexamethylene guanidine phosphate increases stress granule formation in human 3D lung organoids under respiratory syncytial virus infection

• Published in: Ecotoxicology and environmental safety 2022-01, Vol.229, p.113094-113094, Article 113094
• Main Authors: Choi, Seri, Choi, Sunkyung, Choi, Yeongsoo, Cho, Namjoon, Kim, Seung-Yeon, Lee, Chang Hyun, Park, Han-Jin, Oh, Won Keun, Kim, Kee K., Kim, Eun-Mi
• Format: Article
• Language: English
• Subjects: DNA damage; eIF2α; Guanidines - toxicity; Humans; Lung; Lung organoids; Organoids; Polyhexamethylene guanidine phosphate; Pulmonary fibrosis; Respiratory Syncytial Virus Infections; Stress Granules
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2021.113094

Polyhexamethylene guanidine phosphate (PHMG-p), a humidifier disinfectant, is known to cause lung toxicity, including inflammation and pulmonary fibrosis. In this study, we aimed to investigate the effect of PHMG-p on human lung tissue models (2D epithelial cells and 3D organoids) under conditions of oxidative stress and viral infection. The effect of PHMG-p was studied by evaluating the formation of stress granules (SGs), which play a pivotal role in cellular adaptation to various stress conditions. Under oxidative stress and respiratory syncytial virus (RSV) infection, exposure to PHMG-p remarkably increased eIF2α phosphorylation, which is essential for SG-related signalling, and significantly increased SG formation. Furthermore, PHMG-p induced fibrotic gene expression and caused cell death due to severe DNA damage, which was further increased under oxidative stress and RSV infection, indicating that PHMG-p induces severe lung toxicity under stress conditions. Taken together, toxicity evaluation under various stressful conditions is necessary to accurately predict potential lung toxicity of chemicals affecting the respiratory tract. •PHMG-p increases SG formation in oxidative stress and viral infection.•PHMG-p increases cytotoxicity in viral infection.•PHMG-p induces fibrotic gene expression in viral infection.•Human lung organoids are useful model for assessing the lung toxicity potential of chemicals.