Wen Zeng, Zhuyu Deng, Huaying Li, Shuqiang Gao, Rong Ju
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引用次数: 0
Abstract
Background: Hyperoxia-induced injury is a well-recognized cause of bronchopulmonary dysplasia (BPD). Existing research studies have not well elucidated the exact mechanisms underlying hyperoxia-induced cellular damage. This study examines the involvement of the P2X7 receptor (P2X7R) in hyperoxia-induced damage to human pulmonary microvascular endothelial cells (HPMVECs) via the NOD-like receptor family, pyrin domain-containing protein 3 (NLRP3) pathway.
Methods: HPMVECs developing hyperoxia-induced injury were subjected to the treatment of either selective inhibitors or a P2X7R/NLRP3 agonist. Western blot analysis assisted in the quantification of the levels of P2X7R, NLRP3, caspase-1, and gasdermin D (GSDMD). Additionally, the release of TNF-α, IL-1β, and IL-18 was assessed by ELISA and qRT-PCR.
Results: Exposure to hyperoxia diminished cell viability and escalated the levels of P2X7R, caspase-1, NLRP3, GSDMD, and N-terminal-GSDMD. This exposure notably increased the release of TNF-α, IL-1β, and IL-18 in HPMVECs. Notably, the suppression of P2X7R using the inhibitor A438079 decreased pyroptosis and inflammatory responses. Conversely, stimulation of P2X7R by 3'-O-(4-benzoylbenzoyl) adenosine 5'-triphosphate (BzATP) triggered pyroptosis, while inhibition of NLRP3 with glibenclamide ameliorated the damage induced by BzATP.
Conclusions: The P2X7R/NLRP3 pathway crucially affects the hyperoxia-induced inflammation and pyroptosis in HPMVECs, hinting the potential of blocking P2X7R/NLRP3-mediated pyroptotic pathway as a valuable therapeutic strategy for BPD.
期刊介绍:
Open Medicine is an open access journal that provides users with free, instant, and continued access to all content worldwide. The primary goal of the journal has always been a focus on maintaining the high quality of its published content. Its mission is to facilitate the exchange of ideas between medical science researchers from different countries. Papers connected to all fields of medicine and public health are welcomed. Open Medicine accepts submissions of research articles, reviews, case reports, letters to editor and book reviews.