Cargando…
Regulating NLRP3 Inflammasome–Induced Pyroptosis via Nrf2: TBHQ Limits Hyperoxia-Induced Lung Injury in a Mouse Model of Bronchopulmonary Dysplasia
Nuclear factor e2–related factor 2 (Nrf2) plays a key role in cellular resistance to oxidative stress injury. Oxidative stress injury, caused by Nrf2 imbalance, results in increased pyroptosis, DNA damage, and inflammatory activation, which may lead to the arrest of alveolar development and bronchop...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10673969/ https://www.ncbi.nlm.nih.gov/pubmed/37556072 http://dx.doi.org/10.1007/s10753-023-01885-4 |
_version_ | 1785140734962171904 |
---|---|
author | Wang, Minrong Zhang, Feng Ning, Xuemei Wu, Chan Zhou, Yue Gou, Zhixian Fan, Yang Duan, Rongrong Li, Zhongni Shao, Chunyan Lu, Liqun |
author_facet | Wang, Minrong Zhang, Feng Ning, Xuemei Wu, Chan Zhou, Yue Gou, Zhixian Fan, Yang Duan, Rongrong Li, Zhongni Shao, Chunyan Lu, Liqun |
author_sort | Wang, Minrong |
collection | PubMed |
description | Nuclear factor e2–related factor 2 (Nrf2) plays a key role in cellular resistance to oxidative stress injury. Oxidative stress injury, caused by Nrf2 imbalance, results in increased pyroptosis, DNA damage, and inflammatory activation, which may lead to the arrest of alveolar development and bronchopulmonary dysplasia (BPD) in premature infants under hyperoxic conditions. We established a BPD mouse model to investigate the effects of tert-butylhydroquinone (TBHQ), an Nrf2 activator, on oxidative stress injury, pyroptosis, NLRP3 inflammasome activation, and alveolar development. TBHQ reduced abnormal cell death in the lung tissue of BPD mice and restored the number and normal structure of the alveoli. TBHQ administration activated the Nrf2/heme oxygenase-1 (HO-1) signaling pathway, resulting in the decrease in the following: reactive oxygen species (ROS), activation of the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome, and IL-18 and IL-1β expression and activation, as well as inhibition of pyroptosis. In contrast, after Nrf2 gene knockout in BPD mice, there was more severe oxidative stress injury and cell death in the lungs, there were TUNEL + and NLRP3 + co-positive cells in the alveoli, the pyroptosis was significantly increased, and the development of alveoli was significantly blocked. We demonstrated that TBHQ may promote alveolar development by enhancing Nrf2-induced antioxidation in the lung tissue of BPD mice and that the decrease in the NLRP3 inflammasome and pyroptosis caused by Nrf2 activation may be the underlying mechanism. These results suggest that TBHQ is a promising treatment for lung injury in premature infants with hyperoxia. |
format | Online Article Text |
id | pubmed-10673969 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-106739692023-08-09 Regulating NLRP3 Inflammasome–Induced Pyroptosis via Nrf2: TBHQ Limits Hyperoxia-Induced Lung Injury in a Mouse Model of Bronchopulmonary Dysplasia Wang, Minrong Zhang, Feng Ning, Xuemei Wu, Chan Zhou, Yue Gou, Zhixian Fan, Yang Duan, Rongrong Li, Zhongni Shao, Chunyan Lu, Liqun Inflammation Research Nuclear factor e2–related factor 2 (Nrf2) plays a key role in cellular resistance to oxidative stress injury. Oxidative stress injury, caused by Nrf2 imbalance, results in increased pyroptosis, DNA damage, and inflammatory activation, which may lead to the arrest of alveolar development and bronchopulmonary dysplasia (BPD) in premature infants under hyperoxic conditions. We established a BPD mouse model to investigate the effects of tert-butylhydroquinone (TBHQ), an Nrf2 activator, on oxidative stress injury, pyroptosis, NLRP3 inflammasome activation, and alveolar development. TBHQ reduced abnormal cell death in the lung tissue of BPD mice and restored the number and normal structure of the alveoli. TBHQ administration activated the Nrf2/heme oxygenase-1 (HO-1) signaling pathway, resulting in the decrease in the following: reactive oxygen species (ROS), activation of the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome, and IL-18 and IL-1β expression and activation, as well as inhibition of pyroptosis. In contrast, after Nrf2 gene knockout in BPD mice, there was more severe oxidative stress injury and cell death in the lungs, there were TUNEL + and NLRP3 + co-positive cells in the alveoli, the pyroptosis was significantly increased, and the development of alveoli was significantly blocked. We demonstrated that TBHQ may promote alveolar development by enhancing Nrf2-induced antioxidation in the lung tissue of BPD mice and that the decrease in the NLRP3 inflammasome and pyroptosis caused by Nrf2 activation may be the underlying mechanism. These results suggest that TBHQ is a promising treatment for lung injury in premature infants with hyperoxia. Springer US 2023-08-09 2023 /pmc/articles/PMC10673969/ /pubmed/37556072 http://dx.doi.org/10.1007/s10753-023-01885-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Wang, Minrong Zhang, Feng Ning, Xuemei Wu, Chan Zhou, Yue Gou, Zhixian Fan, Yang Duan, Rongrong Li, Zhongni Shao, Chunyan Lu, Liqun Regulating NLRP3 Inflammasome–Induced Pyroptosis via Nrf2: TBHQ Limits Hyperoxia-Induced Lung Injury in a Mouse Model of Bronchopulmonary Dysplasia |
title | Regulating NLRP3 Inflammasome–Induced Pyroptosis via Nrf2: TBHQ Limits Hyperoxia-Induced Lung Injury in a Mouse Model of Bronchopulmonary Dysplasia |
title_full | Regulating NLRP3 Inflammasome–Induced Pyroptosis via Nrf2: TBHQ Limits Hyperoxia-Induced Lung Injury in a Mouse Model of Bronchopulmonary Dysplasia |
title_fullStr | Regulating NLRP3 Inflammasome–Induced Pyroptosis via Nrf2: TBHQ Limits Hyperoxia-Induced Lung Injury in a Mouse Model of Bronchopulmonary Dysplasia |
title_full_unstemmed | Regulating NLRP3 Inflammasome–Induced Pyroptosis via Nrf2: TBHQ Limits Hyperoxia-Induced Lung Injury in a Mouse Model of Bronchopulmonary Dysplasia |
title_short | Regulating NLRP3 Inflammasome–Induced Pyroptosis via Nrf2: TBHQ Limits Hyperoxia-Induced Lung Injury in a Mouse Model of Bronchopulmonary Dysplasia |
title_sort | regulating nlrp3 inflammasome–induced pyroptosis via nrf2: tbhq limits hyperoxia-induced lung injury in a mouse model of bronchopulmonary dysplasia |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10673969/ https://www.ncbi.nlm.nih.gov/pubmed/37556072 http://dx.doi.org/10.1007/s10753-023-01885-4 |
work_keys_str_mv | AT wangminrong regulatingnlrp3inflammasomeinducedpyroptosisvianrf2tbhqlimitshyperoxiainducedlunginjuryinamousemodelofbronchopulmonarydysplasia AT zhangfeng regulatingnlrp3inflammasomeinducedpyroptosisvianrf2tbhqlimitshyperoxiainducedlunginjuryinamousemodelofbronchopulmonarydysplasia AT ningxuemei regulatingnlrp3inflammasomeinducedpyroptosisvianrf2tbhqlimitshyperoxiainducedlunginjuryinamousemodelofbronchopulmonarydysplasia AT wuchan regulatingnlrp3inflammasomeinducedpyroptosisvianrf2tbhqlimitshyperoxiainducedlunginjuryinamousemodelofbronchopulmonarydysplasia AT zhouyue regulatingnlrp3inflammasomeinducedpyroptosisvianrf2tbhqlimitshyperoxiainducedlunginjuryinamousemodelofbronchopulmonarydysplasia AT gouzhixian regulatingnlrp3inflammasomeinducedpyroptosisvianrf2tbhqlimitshyperoxiainducedlunginjuryinamousemodelofbronchopulmonarydysplasia AT fanyang regulatingnlrp3inflammasomeinducedpyroptosisvianrf2tbhqlimitshyperoxiainducedlunginjuryinamousemodelofbronchopulmonarydysplasia AT duanrongrong regulatingnlrp3inflammasomeinducedpyroptosisvianrf2tbhqlimitshyperoxiainducedlunginjuryinamousemodelofbronchopulmonarydysplasia AT lizhongni regulatingnlrp3inflammasomeinducedpyroptosisvianrf2tbhqlimitshyperoxiainducedlunginjuryinamousemodelofbronchopulmonarydysplasia AT shaochunyan regulatingnlrp3inflammasomeinducedpyroptosisvianrf2tbhqlimitshyperoxiainducedlunginjuryinamousemodelofbronchopulmonarydysplasia AT luliqun regulatingnlrp3inflammasomeinducedpyroptosisvianrf2tbhqlimitshyperoxiainducedlunginjuryinamousemodelofbronchopulmonarydysplasia |