Na/K-ATPase suppresses LPS-induced pro-inflammatory signaling through Lyn.
Na/K-ATPase suppresses LPS-induced pro-inflammatory signaling through Lyn.
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DOI：
10.1016/j.isci.2022.104963
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发表时间：
2022-09-16
期刊：
影响因子：
5.8
通讯作者：
Chen, Yiliang
中科院分区：
文献类型：
--
作者：
Zhang, Jue;Chang, Jackie;Beg, Mirza Ahmar;Huang, Wenxin;Zhao, Yiqiong;Dai, Wen;Wu, Xiaopeng;Cui, Weiguo;Pillai, Sneha S.;Lakhani, Hari Vishal;Sodhi, Komal;Shapiro, Joseph I.;Sahoo, Daisy;Zheng, Ze;Silverstein, Roy L.;Chen, Yiliang
Na/K-ATP酶 (NKA) 除了其离子转运功能外，还是通过调节 Src 家族激酶 (SFK) 的信号转导器。信号 NKA 有助于氧化 LDL 诱导的巨噬细胞泡沫细胞形成并与 TLR4 相互作用。然而，其在脂多糖（LPS）诱导的巨噬细胞信号传导和糖酵解开关中的作用仍不清楚。使用来自 NKA α1 单倍体不足小鼠 (NKA α1+/-) 的腹膜巨噬细胞，我们发现 NKA α1 单倍体不足导致 LPS 刺激的 NF-κB 通路、ROS 信号传导和促炎细胞因子增强。腹腔注射LPS导致NKA α1+/-小鼠肺部炎症和损伤更严重，存活率更低。此外，LPS 诱导更高程度的从氧化磷酸化到糖酵解的代谢转换。从机制上讲，NKA α1 与 TLR4 和 Lyn 相互作用。该复合物中 NKA α1 的存在减弱了 LPS 对 Lyn 的激活，从而限制了下游 ROS 和 NF-κB 信号传导。总之，我们证明 NKA α1 通过 Lyn 抑制 LPS 诱导的巨噬细胞促炎症信号传导。 NKA α1 与 TLR4 和 SFK 相互作用 NKA α1 限制巨噬细胞中 LPS 刺激的促炎反应 注射 LPS 的 NKA α1+/- 小鼠表现出更多的肺损伤和更低的存活率免疫学；分子生物学。
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. 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 rate Biological sciences; Immunology; Molecular biology.
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影响因子：
29
作者：
Baker RG;Hayden MS;Ghosh S
通讯作者：
Ghosh S
DOI：
10.1073/pnas.1300290110
发表时间：
2013-06-04
影响因子：
11.1
作者：
Godwin, James W.;Pinto, Alexander R.;Rosenthal, Nadia A.
通讯作者：
Rosenthal, Nadia A.
DOI：
10.1073/pnas.91.8.2965
发表时间：
1994-04-12
影响因子：
11.1
作者：
DEVARAJAN, P;SCARAMUZZINO, DA;MORROW, JS
通讯作者：
MORROW, JS
影响因子：
3.6
作者：
BIEWENGA, J;VANDERENDE, MB;VANROOIJEN, N
通讯作者：
VANROOIJEN, N
影响因子：
15.9
作者：
Febbraio, M;Podrez, EA;Silverstein, RL
通讯作者：
Silverstein, RL