{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T15:03:20Z","timestamp":1793113400138,"version":"4.5.0"},"reference-count":41,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T00:00:00Z","timestamp":1725235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Clinical Research Institute grant","award":["CMCDJ-P-2022-019"],"award-info":[{"award-number":["CMCDJ-P-2022-019"]}]},{"name":"2022 Alumni Research Fund of the Catholic University of Korea College of Medicine Alumni Association","award":["CMCDJ-P-2022-019"],"award-info":[{"award-number":["CMCDJ-P-2022-019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Fine particulate matter, PM2.5, is becoming a major threat to human health, particularly in terms of respiratory diseases. Pyroptosis is a recently discovered and distinct form of cell death, characterized by pore formation in the cell membrane and secretions of proinflammatory cytokines. There has been little research on the effect of PM2.5 on pyroptosis, especially in airway epithelium. We investigated whether PM2.5-related oxidative stress induces pyroptosis in bronchial epithelial cells and defined the underlying mechanisms. Materials and Methods: After exposure of a BEAS-2B cell line to PM2.5 concentration of 20 \u00b5g\/mL, reactive oxygen species (ROS) levels, parameters related to pyroptosis, and NF-\u03baB signaling were measured by Western blotting, immunofluorescence, and ELISA (Enzyme-linked immunosorbent assay). Results: PM2.5 induced pyroptotic cell death, accompanied by LDH (Lactate dehydrogenase) release and increased uptake of propidium iodide in a dose-dependent manner. PM2.5 activated the NLRP3-casp1-gasdermin D pathway, with resulting secretions of the proinflammatory cytokines IL-1\u03b2 and IL-18. The pyroptosis activated by PM2.5 was alleviated significantly by NLRP3 inhibitor. In PM2.5-exposed BEAS-2B cells, levels of intracellular ROS and NF-\u03baB p65 increased. ROS scavenger inhibited the expression of the NLRP3 inflammasome, and the NF-\u03baB inhibitor attenuated pyroptotic cell death triggered by PM2.5 exposure, indicating that the ROS\/NF-\u03baB pathway is involved in PM2.5-induced pyroptosis. Conclusions: These findings show that PM2.5 exposure can cause cell injury by NLRP3-inflammasome-mediated pyroptosis by upregulating the ROS\/NF-\u03baB pathway in airway epithelium.<\/jats:p>","DOI":"10.3390\/medicina60091434","type":"journal-article","created":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T06:51:17Z","timestamp":1725259877000},"page":"1434","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["PM2.5 Induces Pyroptosis via Activation of the ROS\/NF-\u03baB Signaling Pathway in Bronchial Epithelial Cells"],"prefix":"10.3390","volume":"60","author":[{"given":"Ji-Young","family":"Kang","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Jeju National University Hospital, 15 Aran 13-gil, Jeju-si 63241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunsu","family":"Choi","sequence":"additional","affiliation":[{"name":"Clinical Research Institute, Daejeon St. Mary\u2019s Hospital, Daeheung-dong, Jung-gu, Daejeon 34943, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong-Min","family":"Oh","sequence":"additional","affiliation":[{"name":"Clinical Research Institute, Daejeon St. Mary\u2019s Hospital, Daeheung-dong, Jung-gu, Daejeon 34943, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4187-2163","authenticated-orcid":false,"given":"Minsu","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Daejeon St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, 64 Daeheung-ro, Jung-gu, Daejeon 34943, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Chang","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Daejeon St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, 64 Daeheung-ro, Jung-gu, Daejeon 34943, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.toxlet.2018.11.002","article-title":"VCAM-1-mediated neutrophil infiltration exacerbates ambient fine particle-induced lung injury","volume":"302","author":"Cui","year":"2019","journal-title":"Toxicol. Lett."},{"key":"ref_2","unstructured":"Health Effects Institute (2020). State of Global Air 2020, Health Effects Institute."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1289\/ehp.1510810","article-title":"Particulate Matter Exposure and Preterm Birth: Estimates of U.S. Attributable Burden and Economic Costs","volume":"124","author":"Trasande","year":"2016","journal-title":"Environ. Health Perspect."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1016\/S0140-6736(17)30505-6","article-title":"Estimates and 25-year trends of the global burden of disease attributable to ambient air pollution: An analysis of data from the Global Burden of Diseases Study","volume":"389","author":"Cohen","year":"2017","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S67","DOI":"10.1097\/EDE.0000000000001035","article-title":"Association Between Long-term Exposure to PM2.5 and Incidence of Type 2 Diabetes in Taiwan: A National Retrospective Cohort Study","volume":"30","author":"Li","year":"2019","journal-title":"Epidemiology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"107004","DOI":"10.1289\/EHP7246","article-title":"Fine Particulate Matter Exposure and Cancer Incidence: Analysis of SEER Cancer Registry Data from 1992\u20132016","volume":"128","author":"Coleman","year":"2020","journal-title":"Environ. Health Perspect."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"148819","DOI":"10.1016\/j.scitotenv.2021.148819","article-title":"Global burden of COPD attributable to ambient PM2.5 in 204 countries and territories, 1990 to 2019: A systematic analysis for the Global Burden of Disease Study","volume":"796","author":"Yang","year":"2019","journal-title":"Sci. Total. Environ."},{"key":"ref_8","unstructured":"GBD 2019 Risk Factors Collaborators (2019). Global burden of 87 risk factors in 204 countries and territories, 1990\u20132019: A systematic analysis for the Global Burden of Disease Study. Lancet, 396, 1223\u20131249."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"113588","DOI":"10.1016\/j.ecoenv.2022.113588","article-title":"The global burden of disease attributable to ambient fine particulate matter in 204 countries and territories, 1990\u20132019: A systematic analysis of the Global Burden of Disease Study 2019","volume":"238","author":"Sang","year":"2022","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.mrfmmm.2005.06.012","article-title":"Oxidative stress-induced DNA damage by particulate air pollution","volume":"592","author":"Risom","year":"2005","journal-title":"Mutat. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.envres.2019.01.052","article-title":"In vitro evaluation of organic extractable matter from ambient PM2.5 using human bronchial epithelial BEAS-2B cells: Cytotoxicity, oxidative stress, pro-inflammatory response, genotoxicity, and cell cycle deregulation","volume":"171","author":"Abbas","year":"2019","journal-title":"Environ. Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Sachdeva, K., Do, D.C., Zhang, Y., Hu, X., Chen, J., and Gao, P. (2019). Environmental Exposures and Asthma Development: Autophagy, Mitophagy, and Cellular Senescence. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02787"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.anl.2019.11.002","article-title":"Effect of fluticasone propionate on human nasal fibroblasts exposed to urban particulate matter","volume":"47","author":"Kim","year":"2020","journal-title":"Auris Nasus Larynx"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Lee, D.C., Oh, J.M., Choi, H., Kim, S.W., Kim, S.W., Kim, B.G., Cho, J.H., Lee, J., and Kim, J.-S. (2021). Eupatilin Inhibits Reactive Oxygen Species Generation via Akt\/NF-\u03baB\/MAPK Signaling Pathways in Particulate Matter-Exposed Human Bronchial Epithelial Cells. Toxics, 9.","DOI":"10.3390\/toxics9020038"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.trsl.2017.09.005","article-title":"Reactive oxygen species as signaling molecules in the development of lung fibrosis","volume":"190","author":"Chandel","year":"2017","journal-title":"Transl. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5730395","DOI":"10.1155\/2018\/5730395","article-title":"Reactive Oxygen Species in Chronic Obstructive Pulmonary Disease","volume":"2018","author":"Boukhenouna","year":"2018","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Yang, L., Li, C., and Tang, X. (2020). The Impact of PM2.5 on the Host Defense of Respiratory System. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00091"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.toxlet.2020.07.017","article-title":"Urban particulate matter regulates tight junction proteins by inducing oxidative stress via the Akt signal pathway in human nasal epithelial cells","volume":"333","author":"Lee","year":"2020","journal-title":"Toxicol. Lett."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.tibs.2016.10.004","article-title":"Pyroptosis: Gasdermin-Mediated Programmed Necrotic Cell Death","volume":"42","author":"Shi","year":"2017","journal-title":"Trends Biochem. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1007\/s13105-022-00909-1","article-title":"Pyroptosis in inflammation-related respiratory disease","volume":"78","author":"Feng","year":"2022","journal-title":"J. Physiol. Biochem."},{"key":"ref_21","first-page":"757","article-title":"Der f1 induces pyroptosis in human bronchial epithelia via the NLRP3 inflammasome","volume":"41","author":"Tsai","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.jaci.2019.05.006","article-title":"NOD-like receptor family, pyrin domain containing 3 (NLRP3) contributes to inflammation, pyroptosis, and mucin production in human airway epithelium on rhinovirus infection","volume":"144","author":"Liu","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"119090","DOI":"10.1016\/j.lfs.2021.119090","article-title":"Cigarette smoke extract induces pyroptosis in human bronchial epithelial cells through the ROS\/NLRP3\/caspase-1 pathway","volume":"269","author":"Zhang","year":"2021","journal-title":"Life Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1002\/alr.22167","article-title":"The effect of urban particulate matter on cultured human nasal fibroblasts","volume":"8","author":"Lee","year":"2018","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Bang, J., Son, K.H., Heo, H.-R., Park, E., Kwak, H.-J., Uhm, K.-O., Chung, M.-H., Kim, Y.-Y., and Lim, H.J. (2023). Exogenous 8-Hydroxydeoxyguanosine Attenuates PM2.5-Induced Inflammation in Human Bronchial Epithelial Cells by Decreasing NLRP3 Inflammasome Activation. Antioxidants, 12.","DOI":"10.3390\/antiox12061189"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1021\/acsnanoscienceau.2c00059","article-title":"Cell Death Pathways: The Variable Mechanisms Underlying Fine Particulate Matter-Induced Cytotoxicity","volume":"3","author":"Chen","year":"2023","journal-title":"ACS Nanosci. Au"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/s41420-022-00998-3","article-title":"Cell pyroptosis in health and inflammatory diseases","volume":"8","author":"Wu","year":"2022","journal-title":"Cell Death Discov."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"112351","DOI":"10.1016\/j.ecoenv.2021.112351","article-title":"Fine particulate matter-induced lung inflammation is mediated by pyroptosis in mice","volume":"219","author":"Li","year":"2021","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ren, F., Xu, J., Zhang, J., Xu, X., Huang, L., Sun, W., Li, R., and Li, F. (2022). PM2.5 induced lung injury through upregulating ROS-dependent NLRP3 Inflammasome-Mediated Pyroptosis. Immunobiology, 227.","DOI":"10.1016\/j.imbio.2022.152207"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1183\/09031936.00141514","article-title":"The innate immune function of airway epithelial cells in inflammatory lung disease","volume":"45","author":"Hiemstra","year":"2015","journal-title":"Eur. Respir. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.toxlet.2003.12.007","article-title":"The role of nitric oxide in the particulate matter (PM2.5)-induced NFkappaB activation in lung epithelial cells","volume":"148","author":"Nam","year":"2004","journal-title":"Toxicol. Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/nm.3893","article-title":"Inflammasomes: Mechanism of action, role in disease, and therapeutics","volume":"21","author":"Guo","year":"2015","journal-title":"Nat. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.etap.2017.02.011","article-title":"Exposure to PM2.5 induces aberrant activation of NF-\u03baB in human airway epithelial cells by downregulating miR-331 expression","volume":"50","author":"Song","year":"2017","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9940","DOI":"10.1007\/s11356-018-1262-5","article-title":"Cooking oil fume-derived PM2.5 induces apoptosis in A549 cells and MAPK\/NF-\u03baB\/STAT1 pathway activation","volume":"25","author":"Dou","year":"2018","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1165\/rcmb.2004-0309OC","article-title":"Interleukin-1beta causes pulmonary inflammation, emphysema, and airway remodeling in the adult murine lung","volume":"32","author":"Lappalainen","year":"2005","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1016\/S0140-6736(17)32247-X","article-title":"Effect of interleukin-1\u03b2 inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: Exploratory results from a randomised, double-blind, placebo-controlled trial","volume":"390","author":"Ridker","year":"2017","journal-title":"Lancet"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1084\/jem.20031368","article-title":"Interleukin 18 acts on memory T helper cells type 1 to induce airway inflammation and hyperresponsiveness in a naive host mouse","volume":"199","author":"Sugimoto","year":"2004","journal-title":"J. Exp. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"104416","DOI":"10.1016\/j.etap.2024.104416","article-title":"Fine particulate matter PM2.5 and its constituent, hexavalent chromium induce acute cytotoxicity in human airway epithelial cells via inflammasome-mediated pyroptosis","volume":"107","author":"Moonwiriyakit","year":"2024","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Ramos-Martinez, E., Vega-S\u00e1nchez, A.E., P\u00e9rez-Rubio, G., Mejia, M., Buend\u00eda-Rold\u00e1n, I., Gonz\u00e1lez-P\u00e9rez, M.I., Mateos-Toledo, H.N., Andrade, W.A., Falf\u00e1n-Valencia, R., and Rojas-Serrano, J. (2020). Enhanced Activity of NLRP3 Inflammasome in the Lung of Patients with Anti-Synthetase Syndrome. Cells, 12.","DOI":"10.3390\/cells12010060"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Guo, Q., Wu, Y., Hou, Y., Liu, Y., Liu, T., Zhang, H., Fan, C., Guan, H., Li, Y., and Shan, Z. (2018). Cytokine Secretion and Pyroptosis of Thyroid Follicular Cells Mediated by Enhanced NLRP3, NLRP1, NLRC4, and AIM2 Inflammasomes Are Associated With Autoimmune Thyroiditis. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01197"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Fusco, R., Siracusa, R., Genovese, T., Cuzzocrea, S., and Di Paola, R. (2020). Focus on the Role of NLRP3 Inflammasome in Diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124223"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/9\/1434\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:47:13Z","timestamp":1760111233000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/9\/1434"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,2]]},"references-count":41,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["medicina60091434"],"URL":"https:\/\/doi.org\/10.3390\/medicina60091434","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,2]]}}}