The regulatory role of ACP5 in the diesel exhaust particle-induced AHR inflammatory signaling pathway in a human bronchial epithelial cell line
Abstract Exposure to diesel exhaust particles (DEPs), which are major constituents of urban air pollution, is associated with adverse health outcomes. Previous studies have shown that DEPs enhance the expression of pro-inflammatory cytokines and immune responses. However, few studies have focused on...
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Nature Portfolio
2025-03-01
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| Online Access: | https://doi.org/10.1038/s41598-024-84280-9 |
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| author | Aaron Yu Dankyu Yoon Hye Bin An Uimook Choi Hye-Ryeon Heo Dong-Hoon Chae Hyun Sung Park Jae Han Park Myoung Hee Han Jiyoung Heo Keonwoo Cho Ki-Sun Park Hee Min Yoo Hyung-Sik Kim Kyung-Sun Kang Mi-Kyung Oh Hyun Joung Lim Kyung-Rok Yu |
| author_facet | Aaron Yu Dankyu Yoon Hye Bin An Uimook Choi Hye-Ryeon Heo Dong-Hoon Chae Hyun Sung Park Jae Han Park Myoung Hee Han Jiyoung Heo Keonwoo Cho Ki-Sun Park Hee Min Yoo Hyung-Sik Kim Kyung-Sun Kang Mi-Kyung Oh Hyun Joung Lim Kyung-Rok Yu |
| author_sort | Aaron Yu |
| collection | DOAJ |
| description | Abstract Exposure to diesel exhaust particles (DEPs), which are major constituents of urban air pollution, is associated with adverse health outcomes. Previous studies have shown that DEPs enhance the expression of pro-inflammatory cytokines and immune responses. However, few studies have focused on genomic variants that regulate DEP-induced signaling. Here, we identify a frequently found genomic variant, ACP5, in allergic diseases, and establish an ACP5 knock-out (KO) human bronchial epithelial cell line (BEAS-2B) using CRISPR/Cas9 editing to mimic the ACP5 mutation. DEP-induced apoptosis and intracellular reactive oxygen species (ROS) were significantly increased in the ACP5 KO cells compared with controls, suggesting that ACP5 KO cells were at increased risk from DEP exposure. A gene expression profile revealed an activated aryl hydrocarbon receptor (AHR)-CYP1A1 axis followed by upregulated pro-inflammatory signaling. Treatment of a DEP-exposed ACP5 KO BEAS-2B conditioned medium (CM) supernatant induced an inflammatory response and tissue damage in mice, and AHR inhibition effectively prevented inflammation-induced damage, suggesting that AHR-CYP1A1-inflammatory signaling is a prominent mechanism responsible for detrimental effects. Collectively, our findings reveal a novel link between ACP5 KO and the AHR-CYP1A1 inflammatory signaling pathway in DEP-exposed cells, and identify the AHR-CYP1A1 axis as a potential therapeutic target in individuals suffering from DEP-induced toxicity, particularly those with ACP5 mutations. |
| format | Article |
| id | doaj-art-a11c6e7982774ea3aa4ac58f2cbd2432 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-a11c6e7982774ea3aa4ac58f2cbd24322025-08-20T02:31:58ZengNature PortfolioScientific Reports2045-23222025-03-0115111210.1038/s41598-024-84280-9The regulatory role of ACP5 in the diesel exhaust particle-induced AHR inflammatory signaling pathway in a human bronchial epithelial cell lineAaron Yu0Dankyu Yoon1Hye Bin An2Uimook Choi3Hye-Ryeon Heo4Dong-Hoon Chae5Hyun Sung Park6Jae Han Park7Myoung Hee Han8Jiyoung Heo9Keonwoo Cho10Ki-Sun Park11Hee Min Yoo12Hyung-Sik Kim13Kyung-Sun Kang14Mi-Kyung Oh15Hyun Joung Lim16Kyung-Rok Yu17Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National UniversityDivision of Cardiovascular Disease Research, Department of Chronic Disease Convergence, Korea National Institute of HealthDepartment of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National UniversityLaboratory of Clinical Immunology and Microbiology, NIAID, NIHDivision of Cardiovascular Disease Research, Department of Chronic Disease Convergence, Korea National Institute of HealthDepartment of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National UniversityDepartment of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National UniversityDepartment of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National UniversityDepartment of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National UniversityDepartment of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National UniversityDepartment of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National UniversityKM Science Research Division, Korea Institute of Oriental MedicineBiometrology Group, Korea Research Institute of Standards and Science (KRISS)Department of Life Science in Dentistry, School of Dentistry, Pusan National UniversityAdult Stem Cell Research Center and Research, Institute for Veterinary Science, College of Veterinary Medicine, Seoul National UniversityDepartment of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National UniversityDivision of Cardiovascular Disease Research, Department of Chronic Disease Convergence, Korea National Institute of HealthDepartment of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National UniversityAbstract Exposure to diesel exhaust particles (DEPs), which are major constituents of urban air pollution, is associated with adverse health outcomes. Previous studies have shown that DEPs enhance the expression of pro-inflammatory cytokines and immune responses. However, few studies have focused on genomic variants that regulate DEP-induced signaling. Here, we identify a frequently found genomic variant, ACP5, in allergic diseases, and establish an ACP5 knock-out (KO) human bronchial epithelial cell line (BEAS-2B) using CRISPR/Cas9 editing to mimic the ACP5 mutation. DEP-induced apoptosis and intracellular reactive oxygen species (ROS) were significantly increased in the ACP5 KO cells compared with controls, suggesting that ACP5 KO cells were at increased risk from DEP exposure. A gene expression profile revealed an activated aryl hydrocarbon receptor (AHR)-CYP1A1 axis followed by upregulated pro-inflammatory signaling. Treatment of a DEP-exposed ACP5 KO BEAS-2B conditioned medium (CM) supernatant induced an inflammatory response and tissue damage in mice, and AHR inhibition effectively prevented inflammation-induced damage, suggesting that AHR-CYP1A1-inflammatory signaling is a prominent mechanism responsible for detrimental effects. Collectively, our findings reveal a novel link between ACP5 KO and the AHR-CYP1A1 inflammatory signaling pathway in DEP-exposed cells, and identify the AHR-CYP1A1 axis as a potential therapeutic target in individuals suffering from DEP-induced toxicity, particularly those with ACP5 mutations.https://doi.org/10.1038/s41598-024-84280-9ACP5Diesel exhaust particlesBEAS-2BAryl hydrocarbon receptorInflammatory response |
| spellingShingle | Aaron Yu Dankyu Yoon Hye Bin An Uimook Choi Hye-Ryeon Heo Dong-Hoon Chae Hyun Sung Park Jae Han Park Myoung Hee Han Jiyoung Heo Keonwoo Cho Ki-Sun Park Hee Min Yoo Hyung-Sik Kim Kyung-Sun Kang Mi-Kyung Oh Hyun Joung Lim Kyung-Rok Yu The regulatory role of ACP5 in the diesel exhaust particle-induced AHR inflammatory signaling pathway in a human bronchial epithelial cell line Scientific Reports ACP5 Diesel exhaust particles BEAS-2B Aryl hydrocarbon receptor Inflammatory response |
| title | The regulatory role of ACP5 in the diesel exhaust particle-induced AHR inflammatory signaling pathway in a human bronchial epithelial cell line |
| title_full | The regulatory role of ACP5 in the diesel exhaust particle-induced AHR inflammatory signaling pathway in a human bronchial epithelial cell line |
| title_fullStr | The regulatory role of ACP5 in the diesel exhaust particle-induced AHR inflammatory signaling pathway in a human bronchial epithelial cell line |
| title_full_unstemmed | The regulatory role of ACP5 in the diesel exhaust particle-induced AHR inflammatory signaling pathway in a human bronchial epithelial cell line |
| title_short | The regulatory role of ACP5 in the diesel exhaust particle-induced AHR inflammatory signaling pathway in a human bronchial epithelial cell line |
| title_sort | regulatory role of acp5 in the diesel exhaust particle induced ahr inflammatory signaling pathway in a human bronchial epithelial cell line |
| topic | ACP5 Diesel exhaust particles BEAS-2B Aryl hydrocarbon receptor Inflammatory response |
| url | https://doi.org/10.1038/s41598-024-84280-9 |
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