Airborne particulate matter (PM2.5) triggers cornea inflammation and pyroptosis via NLRP3 activation

Liangliang Niu; Liping Li; Chao Xing; Bin Luo; Chunchun Hu; Maomao Song; Jingping Niu; Ye Ruan; Xinghuai Sun; Yuan Lei

doi:10.1016/j.ecoenv.2020.111306

Airborne particulate matter (PM_2.5) triggers cornea inflammation and pyroptosis via NLRP3 activation

Ecotoxicol Environ Saf. 2021 Jan 1:207:111306. doi: 10.1016/j.ecoenv.2020.111306. Epub 2020 Sep 16.

Authors

Liangliang Niu¹, Liping Li¹, Chao Xing², Bin Luo³, Chunchun Hu¹, Maomao Song¹, Jingping Niu⁴, Ye Ruan⁵, Xinghuai Sun⁶, Yuan Lei⁷

Affiliations

¹ Department of Ophthalmology & Visual Science, Eye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, 200031, China.
² Animal research center, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, 200031, China.
³ Institute of Occupational Health and Environmental Health, School of Public Health, Lanzhou University, Lanzhou, 730000, Gansu, China; Shanghai Key Laboratory of Meteorology and Health, Shanghai, 200030, China.
⁴ Institute of Occupational Health and Environmental Health, School of Public Health, Lanzhou University, Lanzhou, 730000, Gansu, China.
⁵ Institute of Occupational Health and Environmental Health, School of Public Health, Lanzhou University, Lanzhou, 730000, Gansu, China. Electronic address: ruany@lzu.edu.cn.
⁶ Department of Ophthalmology & Visual Science, Eye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, 200031, China; Key Laboratory of Myopia, Chinese Academy of Medical Sciences (Fudan University), And Shanghai Key Laboratory of Visual Impairment and Restoration (Fudan University), Shanghai, 200031, China; State Key Laboratory of Medical Neurobiology, Institute of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai 200031, China. Electronic address: xhsun@shmu.edu.cn.
⁷ Department of Ophthalmology & Visual Science, Eye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, 200031, China; Key Laboratory of Myopia, Chinese Academy of Medical Sciences (Fudan University), And Shanghai Key Laboratory of Visual Impairment and Restoration (Fudan University), Shanghai, 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai 200031, China. Electronic address: lilian0167@hotmail.com.

PMID: 32949934
DOI: 10.1016/j.ecoenv.2020.111306

Abstract

Although studies have demonstrated that fine particulate matter (PM_2.5) induces ocular surface damage, PM2.5 exposure causes cornea toxicity is not entirely clear. The aim of this study is to investigate the role of the nod-like receptor family pyrin domain containing three (NLRP3) inflammasome-mediated pyroptosis in PM_2.5-related corneal toxicity. Human corneal epithelial cells (HCECs) were exposed to different concentrations of PM_2.5, and the cell viability, expressions of NLRP3 inflammasome mediated pyroptosis axis molecules and intracellular reactive oxygen species (ROS) formation were measured in HCECs. Animal experiments were undertaken to topically apply PM_2.5 suspension to mouse eyes for three months and the pyroptosis related molecules in the mouse corneas were measured. RESULTS: Our results showed a dose-dependent decrease of HCEC viability in the PM_2.5-treated cells. NLRP3 inflammasome-mediated pyroptosis axis (NLRP3, ASC, GSDMD, caspase-1, IL-1β, and IL-18) were activated in the PM_2.5-treated HCECs, accompanied by increased ROS formation. Further in vivo study confirmed the activation of this pathway in the mouse corneas exposed to PM_2.5. In conclusion, this study provids novel evidence that PM_2.5 induces corneal toxicity by triggering cell pyroptosis.

Keywords: Cornea; Fine particulate matter; Inflammation; NLRP3 inflammasome; Pyroptosis.

MeSH terms

Animals
Caspase 1 / metabolism
Cell Line
Cell Survival / drug effects
Cornea / drug effects*
Cornea / pathology
Epithelial Cells / drug effects*
Epithelial Cells / immunology
Epithelial Cells / metabolism
Epithelial Cells / pathology
Humans
Inflammasomes / metabolism*
Inflammation
Interleukin-18 / metabolism
Interleukin-1beta / metabolism
Mice
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
Particulate Matter / toxicity*
Pyroptosis / drug effects*
Reactive Oxygen Species / metabolism

Substances

IL18 protein, human
IL1B protein, human
Inflammasomes
Interleukin-18
Interleukin-1beta
NLR Family, Pyrin Domain-Containing 3 Protein
Particulate Matter
Reactive Oxygen Species
Caspase 1