Na/K-ATPase suppresses LPS-induced pro-inflammatory signaling through Lyn

Jue Zhang, Jackie Chang, Mirza Ahmar Beg, Wenxin Huang, Yiqiong Zhao, Wen Dai, Xiaopeng Wu, Weiguo Cui, Sneha S. Pillai, Hari Vishal Lakhani, Komal Sodhi, Joseph I. Shapiro, Daisy Sahoo, Ze Zheng, Roy L. Silverstein, Yiliang Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number104963
Issue number9
StatePublished - Sep 16 2022


  • Biological sciences
  • immunology
  • molecular biology

ASJC Scopus subject areas

  • General


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