TBHQ Alleviates Particulate Matter-Induced Pyroptosis in Human Nasal Epithelial Cells

Overview

Journal Toxics

Date 2024 Jun 26

PMID 38922087

Authors

Ji-Sun Kim

Hyunsu Choi

Jeong-Min Oh

Sung Won Kim

Soo Whan Kim

Byung Guk Kim

Jin Hee Cho

Joohyung Lee

Dong Chang Lee

Affiliations

Soon will be listed here.

Abstract

Pyroptosis represents a type of cell death mechanism notable for its cell membrane disruption and the subsequent release of proinflammatory cytokines. The Nod-like receptor family pyrin domain containing inflammasome 3 (NLRP3) plays a critical role in the pyroptosis mechanism associated with various diseases resulting from particulate matter (PM) exposure. Tert-butylhydroquinone (tBHQ) is a synthetic antioxidant commonly used in a variety of foods and products. The aim of this study is to examine the potential of tBHQ as a therapeutic agent for managing sinonasal diseases induced by PM exposure. The occurrence of NLRP3 inflammasome-dependent pyroptosis in RPMI 2650 cells treated with PM < 4 µm in size was confirmed using Western blot analysis and enzyme-linked immunosorbent assay results for the pyroptosis metabolites IL-1β and IL-18. In addition, the inhibitory effect of tBHQ on PM-induced pyroptosis was confirmed using Western blot and immunofluorescence techniques. The inhibition of tBHQ-mediated pyroptosis was abolished upon nuclear factor erythroid 2-related factor 2 (Nrf2) knockdown, indicating its involvement in the antioxidant mechanism. tBHQ showed potential as a therapeutic agent for sinonasal diseases induced by PM because NLRP3 inflammasome activation was effectively suppressed via the Nrf2 pathway.

References

Moller P, Folkmann J, Forchhammer L, Brauner E, Danielsen P, Risom L . Air pollution, oxidative damage to DNA, and carcinogenesis. Cancer Lett. 2008; 266(1):84-97. DOI: 10.1016/j.canlet.2008.02.030. View

Gao L, Qin J, Shi J, Jiang T, Wang F, Xie C . Fine particulate matter exposure aggravates ischemic injury via NLRP3 inflammasome activation and pyroptosis. CNS Neurosci Ther. 2022; 28(7):1045-1058. PMC: 9160454. DOI: 10.1111/cns.13837. View

Penard-Morand C, Raherison C, Charpin D, Kopferschmitt C, Lavaud F, Caillaud D . Long-term exposure to close-proximity air pollution and asthma and allergies in urban children. Eur Respir J. 2010; 36(1):33-40. DOI: 10.1183/09031936.00116109. View

He Y, Hara H, Nunez G . Mechanism and Regulation of NLRP3 Inflammasome Activation. Trends Biochem Sci. 2016; 41(12):1012-1021. PMC: 5123939. DOI: 10.1016/j.tibs.2016.09.002. View

Bergsbaken T, Fink S, Cookson B . Pyroptosis: host cell death and inflammation. Nat Rev Microbiol. 2009; 7(2):99-109. PMC: 2910423. DOI: 10.1038/nrmicro2070. View

Zheng R, Tao L, Jian H, Chang Y, Cheng Y, Feng Y . NLRP3 inflammasome activation and lung fibrosis caused by airborne fine particulate matter. Ecotoxicol Environ Saf. 2018; 163:612-619. DOI: 10.1016/j.ecoenv.2018.07.076. View

Osornio-Vargas A, Bonner J, Alfaro-Moreno E, Martinez L, Garcia-Cuellar C, Ponce-de-Leon Rosales S . Proinflammatory and cytotoxic effects of Mexico City air pollution particulate matter in vitro are dependent on particle size and composition. Environ Health Perspect. 2003; 111(10):1289-93. PMC: 1241608. DOI: 10.1289/ehp.5913. View

Nguyen T, Nioi P, Pickett C . The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem. 2009; 284(20):13291-5. PMC: 2679427. DOI: 10.1074/jbc.R900010200. View

Martinon F, Burns K, Tschopp J . The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell. 2002; 10(2):417-26. DOI: 10.1016/s1097-2765(02)00599-3. View

10.

Li S, Li J, Shen C, Zhang X, Sun S, Cho M . tert-Butylhydroquinone (tBHQ) protects hepatocytes against lipotoxicity via inducing autophagy independently of Nrf2 activation. Biochim Biophys Acta. 2013; 1841(1):22-33. PMC: 3884638. DOI: 10.1016/j.bbalip.2013.09.004. View

11.

Su R, Jin X, Zhang W, Li Z, Liu X, Ren J . Particulate matter exposure induces the autophagy of macrophages via oxidative stress-mediated PI3K/AKT/mTOR pathway. Chemosphere. 2016; 167:444-453. DOI: 10.1016/j.chemosphere.2016.10.024. View

12.

Hurtado-Navarro L, Angosto-Bazarra D, Pelegrin P, Baroja-Mazo A, Cuevas S . NLRP3 Inflammasome and Pyroptosis in Liver Pathophysiology: The Emerging Relevance of Nrf2 Inducers. Antioxidants (Basel). 2022; 11(5). PMC: 9137763. DOI: 10.3390/antiox11050870. View

13.

Khezerlou A, Akhlaghi A, Mirza Alizadeh A, Dehghan P, Maleki P . Alarming impact of the excessive use of tert-butylhydroquinone in food products: A narrative review. Toxicol Rep. 2022; 9:1066-1075. PMC: 9764193. DOI: 10.1016/j.toxrep.2022.04.027. View

14.

Cookson B, Brennan M . Pro-inflammatory programmed cell death. Trends Microbiol. 2001; 9(3):113-4. DOI: 10.1016/s0966-842x(00)01936-3. View

15.

Brown J, Gordon T, Price O, Asgharian B . Thoracic and respirable particle definitions for human health risk assessment. Part Fibre Toxicol. 2013; 10:12. PMC: 3640939. DOI: 10.1186/1743-8977-10-12. View

16.

Xu X, Liu A, Hu S, Ares I, Martinez-Larranaga M, Wang X . Synthetic phenolic antioxidants: Metabolism, hazards and mechanism of action. Food Chem. 2021; 353:129488. DOI: 10.1016/j.foodchem.2021.129488. View

17.

Duan X, Li J, Xing X, Zhang Y, Li W, Zhao L . Antioxidant tert-butylhydroquinone ameliorates arsenic-induced intracellular damages and apoptosis through induction of Nrf2-dependent antioxidant responses as well as stabilization of anti-apoptotic factor Bcl-2 in human keratinocytes. Free Radic Biol Med. 2016; 94:74-87. DOI: 10.1016/j.freeradbiomed.2016.02.009. View

18.

Hong Z, Guo Z, Zhang R, Xu J, Dong W, Zhuang G . Airborne Fine Particulate Matter Induces Oxidative Stress and Inflammation in Human Nasal Epithelial Cells. Tohoku J Exp Med. 2016; 239(2):117-25. DOI: 10.1620/tjem.239.117. View

19.

Xi M, Shen D, Dai P, Han G, Li C . TBHQ alleviates pyroptosis and necroptosis in chicken alveolar epithelial cells induced by fine particulate matter from broiler houses. Poult Sci. 2021; 101(2):101593. PMC: 8717573. DOI: 10.1016/j.psj.2021.101593. View

20.

Wang L, Manji G, Grenier J, Al-Garawi A, Merriam S, Lora J . PYPAF7, a novel PYRIN-containing Apaf1-like protein that regulates activation of NF-kappa B and caspase-1-dependent cytokine processing. J Biol Chem. 2002; 277(33):29874-80. DOI: 10.1074/jbc.M203915200. View