Estrogen-regulated STAT1 activation promotes TLR8 expression to facilitate signaling via microRNA-21 in systemic lupus erythematosus.
Estrogen-regulated STAT1 activation promotes TLR8 expression to facilitate signaling via microRNA-21 in systemic lupus erythematosus.
复制标题
DOI：
10.1016/j.clim.2016.12.005
复制
发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Jarjour WN
中科院分区：
文献类型：
--
作者：
Young NA;Valiente GR;Hampton JM;Wu LC;Burd CJ;Willis WL;Bruss M;Steigelman H;Gotsatsenko M;Amici SA;Severin M;Claverie LM;Guerau-de-Arellano M;Lovett-Racke A;Ardoin S;Jarjour WN
最近的研究表明先天免疫与系统性红斑狼疮(SLE)的发病机制有关。Toll样受体(Toll-like Receptor，TLR)8受雌激素调节并与病毒单链RNA结合以刺激天然免疫反应，但最近的研究表明，细胞外小泡(EV)中的microRNA(MiR)-21也可以触发该受体。我们的目的是检测TLR8的表达/激活，以更好地了解SLE中涉及TLR8的性别偏见反应。我们的数据确定了一种促进STAT1表达的雌激素反应元件，并证明了雌激素刺激下TLR8依赖于STAT1的转录激活。代替病毒单链RNA的激活，我们探索了EV包裹的miR-21作为内源配体，并在体外观察到TLR8和细胞因子的诱导表达。此外，细胞外miR的检测主要在EVS内发现。因此，就像细胞因子或趋化因子一样，EV包裹的miR-21作为TLR8的内源性配体，可以作为炎症信号分子或miRokine发挥作用。总之，我们的数据阐明了系统性红斑狼疮中一种新的先天炎症途径。
Recent studies implicate innate immunity to systemic lupus erythematosus (SLE) pathogenesis. Toll-like receptor (TLR)8 is estrogen-regulated and binds viral ssRNA to stimulate innate immune responses, but recent work indicates that microRNA (miR)-21 within extracellular vesicles (EVs) can also trigger this receptor. Our objective was to examine TLR8 expression/activation to better understand sex-biased responses involving TLR8 in SLE. Our data identify an estrogen response element that promotes STAT1 expression and demonstrate STAT1-dependent transcriptional activation of TLR8 with estrogen stimulation. In lieu of viral ssRNA activation, we explored EV-encapsulated miR-21 as an endogenous ligand and observed induction of both TLR8 and cytokine expression in vitro. Moreover, extracellular miR detection was found predominantly within EVs. Thus, just as a cytokine or chemokine, EV-encapsulated miR-21 can act as an inflammatory signaling molecule, or miRokine, by virtue of being an endogenous ligand of TLR8. Collectively, our data elucidates a novel innate inflammatory pathway in SLE.
登录
查看更多内容
影响因子：
3.7
作者：
Jablonski KA;Amici SA;Webb LM;Ruiz-Rosado Jde D;Popovich PG;Partida-Sanchez S;Guerau-de-Arellano M
通讯作者：
Guerau-de-Arellano M
影响因子：
14.9
作者：
Bartlett DW;Davis ME
通讯作者：
Davis ME
影响因子：
14.9
作者：
Bhat-Nakshatri P;Wang G;Collins NR;Thomson MJ;Geistlinger TR;Carroll JS;Brown M;Hammond S;Srour EF;Liu Y;Nakshatri H
通讯作者：
Nakshatri H
影响因子：
7.7
作者：
Gysemans, CA;Ladrière, L;Mathieu, C
通讯作者：
Mathieu, C
影响因子：
9.3
作者：
El-Hefnawy, T;Raja, S;Godfrey, TE
通讯作者：
Godfrey, TE