| First Author | Zhang J | Year | 2022 |
| Journal | iScience | Volume | 25 |
| Issue | 9 | Pages | 104963 |
| PubMed ID | 36072548 | Mgi Jnum | J:328242 |
| Mgi Id | MGI:7335659 | Doi | 10.1016/j.isci.2022.104963 |
| Citation | Zhang J, et al. (2022) Na/K-ATPase suppresses LPS-induced pro-inflammatory signaling through Lyn. iScience 25(9):104963 |
| abstractText | 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 alpha1 haploinsufficient mice (NKA alpha1(+/-)), we found that NKA alpha1 haploinsufficiency led to enhanced LPS-stimulated NF-kappaB 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 alpha1(+/-) mice. Additionally, LPS induced a higher extent of the metabolic switch from oxidative phosphorylation to glycolysis. Mechanistically, NKA alpha1 interacted with TLR4 and Lyn. The presence of NKA alpha1 in this complex attenuated Lyn activation by LPS, which subsequently restricted the downstream ROS and NF-kappaB signaling. In conclusion, we demonstrated that NKA alpha1 suppresses LPS-induced macrophage pro-inflammatory signaling through Lyn. |
