A Toll‐like receptor 2 ligand, Pam3CSK4, augments interferon‐γ‐induced nitric oxide production via a physical association between MyD88 and interferon‐γ receptor in vascular endothelial cells
A Toll‐like receptor 2 ligand, Pam3CSK4, augments interferon‐γ‐induced nitric oxide production via a physical association between MyD88 and interferon‐γ receptor in vascular endothelial cells
复制标题
Toll 样受体 2 配体 Pam3CSK4 通过 MyD88 和血管内皮细胞中干扰素 γ 受体之间的物理关联增强干扰素 γ 诱导的一氧化氮产生
作者：
Bilegtsaikhan Tsolmongyn;N. Koide;Ulziisaikhan Jambalganiin;E. Odkhuu;Y. Naiki;T. Komatsu;T. Yoshida;T. Yokochi
研究了Toll样受体2（TLR 2）配体Pam 3CSK 4对小鼠血管内皮END-D细胞中干扰素-γ（IFN-γ）诱导的一氧化氮（NO）产生的影响。用Pam 3CSK 4预处理或后处理通过增强诱导型NO合酶（iNOS）蛋白和mRNA的表达来增强IFN-γ诱导的NO产生。Pam 3CSK 4增强Janus激酶1和2的磷酸化，随后增强信号转导和转录激活因子1（STAT 1）在酪氨酸701处的磷酸化。随后，增强的STAT 1活化增强IFN-γ诱导的IFN-调节因子1表达，导致iNOS表达。Pam 3CSK 4还诱导p38的活化和随后的STAT 1在丝氨酸727处的磷酸化。药理学p38抑制剂消除了Pam 3CSK 4对IFN-γ诱导的NO产生的增强作用。令人惊讶的是，Pam 3CSK 4增强了MyD 88和IFN-γ受体的物理结合。总之，这些发现表明Pam 3CSK 4通过MyD 88和IFN-γ受体α之间的物理关联以及p38依赖性丝氨酸727 STAT 1磷酸化上调血管内皮细胞中的IFN-γ信号传导。
The effect of Pam3CSK4, a Toll‐like receptor 2 (TLR2) ligand, on interferon‐γ (IFN‐γ) ‐induced nitric oxide (NO) production in mouse vascular endothelial END‐D cells was studied. Pre‐treatment or post‐treatment with Pam3CSK4 augmented IFN‐γ‐induced NO production via enhanced expression of an inducible NO synthase (iNOS) protein and mRNA. Pam3CSK4 augmented phosphorylation of Janus kinase 1 and 2, followed by enhanced phosphorylation of signal transducer and activator of transcription 1 (STAT1) at tyrosine 701. Subsequently, the enhanced STAT1 activation augmented IFN‐γ‐induced IFN‐regulatory factor 1 expression leading to the iNOS expression. Pam3CSK4 also induced the activation of p38 and subsequent phosphorylation of STAT1 at serine 727. A pharmacological p38 inhibitor abolished the augmentation of IFN‐γ‐induced NO production by Pam3CSK4. Surprisingly, Pam3CSK4 enhanced a physical association of MyD88 and IFN‐γ receptor. Together, these findings suggest that Pam3CSK4 up‐regulates IFN‐γ signalling in vascular endothelial cells via the physical association between MyD88 and IFN‐γ receptor α, and p38‐dependent serine 727 STAT1 phosphorylation.
影响因子：
2.9
作者：
GREEN, LC;WAGNER, DA;TANNENBAUM, SR
通讯作者：
TANNENBAUM, SR
影响因子：
32.4
作者：
Hu X;Ivashkiv LB
通讯作者：
Ivashkiv LB