文章基本信息

标题：Na/K-ATPase suppresses LPS-induced pro-inflammatory signaling through Lyn
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作者：Jue Zhang ; Jackie Chang ; Mirza Ahmar Beg 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：9
页码：1-20
DOI：10.1016/j.isci.2022.104963
语种：English
出版社：Elsevier
摘要：SummaryNa/K-ATPase (NKA), besides its ion transporter function, is a signal transducer by regulating Src family kinases (SFK). The signaling NKA contributes to oxidized LDL-induced macrophage foam cell formation and interacts with TLR4. However, its role in lipopolysaccharides (LPS)-induced signaling and glycolytic switch in macrophages remains unclear. Using peritoneal macrophages from NKA α1 haploinsufficient mice (NKA α1+/−), we found that NKA α1 haploinsufficiency led to enhanced LPS-stimulated NF-κB pathway, ROS signaling, and pro-inflammatory cytokines. Intraperitoneal injection of LPS resulted in more severe lung inflammation and injury with lower survival rate in NKA α1+/−mice. Additionally, LPS induced a higher extent of the metabolic switch from oxidative phosphorylation to glycolysis. Mechanistically, NKA α1 interacted with TLR4 and Lyn. The presence of NKA α1 in this complex attenuated Lyn activation by LPS, which subsequently restricted the downstream ROS and NF-κB signaling. In conclusion, we demonstrated that NKA α1 suppresses LPS-induced macrophage pro-inflammatory signaling through Lyn.Graphical abstractDisplay OmittedHighlights•NKA α1 interacts with TLR4 and SFKs•NKA α1 restricts LPS-stimulated pro-inflammatory responses in macrophages•NKA α1+/−mice injected with LPS show more lung injury and lower survival rateBiological sciences; Immunology; Molecular biology.