Na/K-ATPase suppresses LPS-induced pro-inflammatory signaling through Lyn. iScience 2022 Sep 16;25(9):104963
Date
09/09/2022Pubmed ID
36072548Pubmed Central ID
PMC9442361DOI
10.1016/j.isci.2022.104963Scopus ID
2-s2.0-85137074779 (requires institutional sign-in at Scopus site) 7 CitationsAbstract
Na/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.
Author List
Zhang J, Chang J, Beg MA, Huang W, Zhao Y, Dai W, Wu X, Cui W, Pillai SS, Lakhani HV, Sodhi K, Shapiro JI, Sahoo D, Zheng Z, Silverstein RL, Chen YAuthors
Yiliang Chen PhD Assistant Professor in the Medicine department at Medical College of WisconsinDaisy Sahoo PhD Dean, Professor in the Medicine department at Medical College of Wisconsin
Roy L. Silverstein MD Professor in the Medicine department at Medical College of Wisconsin
Ze Zheng PhD Assistant Professor in the Medicine department at Medical College of Wisconsin
