Nrf2 regulates the activation of THP-1 cells induced by chloral hydrate
Trichloroethylene (TCE) triggers a severe hypersensitivity syndrome in the occupational population dependent on dendritic cells (DCs). Chloral hydrate (CH), the major oxidative metabolite of TCE, has been proved to be the culprit causative substance of TCE-induced hypersensitivity by human patch tes...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651323003457 |
| _version_ | 1797840556921978880 |
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| author | Jinfeng Zhao Shiyu Yan Xue Ma Yanqing Song Yao Pan |
| author_facet | Jinfeng Zhao Shiyu Yan Xue Ma Yanqing Song Yao Pan |
| author_sort | Jinfeng Zhao |
| collection | DOAJ |
| description | Trichloroethylene (TCE) triggers a severe hypersensitivity syndrome in the occupational population dependent on dendritic cells (DCs). Chloral hydrate (CH), the major oxidative metabolite of TCE, has been proved to be the culprit causative substance of TCE-induced hypersensitivity by human patch tests. Because redox imbalance is essential for chemical sensitizers-induced maturation of DCs, we predicted that CH would activate DCs by the nuclear factor E2-related factor 2 (Nrf2)-mediated antioxidant response. This study selected THP-1 cells as the in vitro DC model, and we evaluated the cell activation markers, intracellular oxidative stress, and Nrf2 pathway related genes expression in response to CH in THP-1 cells. CH displayed significant stimulation of THP-1 cells activation, including CD54 and CD86 expression, IL-8 release, and cell migration, and damaged the redox balance by triggering ROS generation, GSH consumption, and antioxidase activities modulation. The levels of Nrf2 and its downstream genes (HO-1 and NQO1) in mRNA and protein expressions were upregulated by CH, and CH also promoted the nuclear translocation of Nrf2. Subsequently, we investigated the effects of antioxidant on Nrf2-mediated cell defense in CH treated cells. Pretreatment with curcumin dramatically reduced cell activation and oxidative stress triggered by CH in THP-1 cells. We also confirmed the specific role of Nrf2 in CH-induced cell activation using NRF2-knockout cells. Deficiency of Nrf2 inhibited cell activation and downregulated HO-1 and NQO1 expression in CH-challenged cells. These findings suggest that Nrf2-dependent redox homeostasis plays a pivotal role in CH-induced activation of THP-1 cells, thereby providing new knowledge of the allergen as well as the molecular mechanism involving in TCE-induce hypersensitivity syndrome. |
| first_indexed | 2024-04-09T16:17:17Z |
| format | Article |
| id | doaj.art-a54a902902d84ec5a1c07542ef2b4bb8 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-09T16:17:17Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-a54a902902d84ec5a1c07542ef2b4bb82023-04-24T04:36:46ZengElsevierEcotoxicology and Environmental Safety0147-65132023-05-01256114841Nrf2 regulates the activation of THP-1 cells induced by chloral hydrateJinfeng Zhao0Shiyu Yan1Xue Ma2Yanqing Song3Yao Pan4Department of Cosmetics, College of Chemistry and Materials Engineering, Beijing Technology and Business University, Beijing 100048, China; Beijing Key Laboratory of Plant Research and Development, Beijing 100048, ChinaDepartment of Cosmetics, College of Chemistry and Materials Engineering, Beijing Technology and Business University, Beijing 100048, China; Beijing Key Laboratory of Plant Research and Development, Beijing 100048, ChinaDepartment of Cosmetics, College of Chemistry and Materials Engineering, Beijing Technology and Business University, Beijing 100048, China; Beijing Key Laboratory of Plant Research and Development, Beijing 100048, ChinaDepartment of Cosmetics, College of Chemistry and Materials Engineering, Beijing Technology and Business University, Beijing 100048, China; Beijing Key Laboratory of Plant Research and Development, Beijing 100048, ChinaDepartment of Cosmetics, College of Chemistry and Materials Engineering, Beijing Technology and Business University, Beijing 100048, China; Beijing Key Laboratory of Plant Research and Development, Beijing 100048, China; Correspondence to: Department of Cosmetics, College of Chemistry and Materials Engineering, Beijing Technology and Business University, 11 Fu Cheng Road, Hai Dian District, Beijing 100048, China.Trichloroethylene (TCE) triggers a severe hypersensitivity syndrome in the occupational population dependent on dendritic cells (DCs). Chloral hydrate (CH), the major oxidative metabolite of TCE, has been proved to be the culprit causative substance of TCE-induced hypersensitivity by human patch tests. Because redox imbalance is essential for chemical sensitizers-induced maturation of DCs, we predicted that CH would activate DCs by the nuclear factor E2-related factor 2 (Nrf2)-mediated antioxidant response. This study selected THP-1 cells as the in vitro DC model, and we evaluated the cell activation markers, intracellular oxidative stress, and Nrf2 pathway related genes expression in response to CH in THP-1 cells. CH displayed significant stimulation of THP-1 cells activation, including CD54 and CD86 expression, IL-8 release, and cell migration, and damaged the redox balance by triggering ROS generation, GSH consumption, and antioxidase activities modulation. The levels of Nrf2 and its downstream genes (HO-1 and NQO1) in mRNA and protein expressions were upregulated by CH, and CH also promoted the nuclear translocation of Nrf2. Subsequently, we investigated the effects of antioxidant on Nrf2-mediated cell defense in CH treated cells. Pretreatment with curcumin dramatically reduced cell activation and oxidative stress triggered by CH in THP-1 cells. We also confirmed the specific role of Nrf2 in CH-induced cell activation using NRF2-knockout cells. Deficiency of Nrf2 inhibited cell activation and downregulated HO-1 and NQO1 expression in CH-challenged cells. These findings suggest that Nrf2-dependent redox homeostasis plays a pivotal role in CH-induced activation of THP-1 cells, thereby providing new knowledge of the allergen as well as the molecular mechanism involving in TCE-induce hypersensitivity syndrome.http://www.sciencedirect.com/science/article/pii/S0147651323003457Chloral hydrateTHP-1Nuclear factor-erythroid 2-related factor 2CurcuminOxidative stress |
| spellingShingle | Jinfeng Zhao Shiyu Yan Xue Ma Yanqing Song Yao Pan Nrf2 regulates the activation of THP-1 cells induced by chloral hydrate Ecotoxicology and Environmental Safety Chloral hydrate THP-1 Nuclear factor-erythroid 2-related factor 2 Curcumin Oxidative stress |
| title | Nrf2 regulates the activation of THP-1 cells induced by chloral hydrate |
| title_full | Nrf2 regulates the activation of THP-1 cells induced by chloral hydrate |
| title_fullStr | Nrf2 regulates the activation of THP-1 cells induced by chloral hydrate |
| title_full_unstemmed | Nrf2 regulates the activation of THP-1 cells induced by chloral hydrate |
| title_short | Nrf2 regulates the activation of THP-1 cells induced by chloral hydrate |
| title_sort | nrf2 regulates the activation of thp 1 cells induced by chloral hydrate |
| topic | Chloral hydrate THP-1 Nuclear factor-erythroid 2-related factor 2 Curcumin Oxidative stress |
| url | http://www.sciencedirect.com/science/article/pii/S0147651323003457 |
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