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The mechanisms behind this damage have not been fully explained. This study investigated two types of cellular damage (inflammation and pyroptosis) induced by PM2.5, focusing on their relationship with two organelles (the endoplasmic reticulum and mitochondria). Animal models have demonstrated that PM2.5 induces excessive endoplasmic reticulum stress (ER stress), which is a significant cause of lung damage in rats. This was confirmed by pretreatment with an ER stress inhibitor (4-Phenylbutyric acid, 4-PBA). We found that, in vitro, the intracellular Ca2+ ([Ca2+]i) dysregulation induced by PM2.5 in rat alveolar macrophages was associated with ER stress. Changes in mitochondria-associated membranes (MAMs) result in abnormal mitochondrial function. This further induced the massive expression of NLRP3 and GSDMD-N, which was detrimental to cell survival. In conclusion, our findings provide valuable insights into the relationship between [Ca2+]i dysregulation, mitochondrial damage, inflammation and pyroptosis under PM2.5-induced ER stress conditions. Their interactions ultimately have an impact on respiratory health.<\/jats:p>","DOI":"10.3390\/biom14091135","type":"journal-article","created":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T03:04:18Z","timestamp":1725851058000},"page":"1135","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Attenuation of PM2.5-Induced Lung Injury by 4-Phenylbutyric Acid: Maintenance of [Ca2+]i Stability between Endoplasmic Reticulum and Mitochondria"],"prefix":"10.3390","volume":"14","author":[{"given":"Zhenhua","family":"Ma","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China"},{"name":"Institute of Animal Science, Ningxia Academy of Agriculture and Forestry Sciences, Yinchuan 750002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Du","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yize","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunna","family":"Jia","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"Liang","sequence":"additional","affiliation":[{"name":"Institute of Animal Science, Ningxia Academy of Agriculture and Forestry Sciences, Yinchuan 750002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5701-6685","authenticated-orcid":false,"given":"Yunhang","family":"Gao","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"170620","DOI":"10.1016\/j.scitotenv.2024.170620","article-title":"Insights into PM2.5 pollution of four small and medium-sized cities in Chinese representative regions: Chemical compositions, sources and health risks","volume":"918","author":"Liu","year":"2024","journal-title":"Sci. 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