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

Abstract

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.

• Authors: Seri Choi, Sunkyung Choi, Yeongsoo Choi, Namjoon Cho, Seung-Yeon Kim, Chang Hyun Lee, Han-Jin Park, Won Keun Oh, Kee K Kim, Eun-Mi Kim
• Journal: Ecotoxicology and environmental safety (Ecotoxicol Environ Saf) Vol. 229 Pg. 113094 (Jan 01 2022) ISSN: 1090-2414 [Electronic] Netherlands
• PMID: 34942421 (Publication Type: Journal Article)
• Copyright: Copyright © 2021. Published by Elsevier Inc.

Chemical References

• Guanidines
• polyhexamethyleneguanidine

Topics

• Guanidines (toxicity)
• Humans
• Lung
• Organoids
• Respiratory Syncytial Virus Infections
• Stress Granules