当前位置: X-MOL 学术Inflamm. Res. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Human host defense peptide LL-37 facilitates double-stranded RNA pro-inflammatory signaling through up-regulation of TLR3 expression in vascular smooth muscle cells.
Inflammation Research ( IF 4.8 ) Pub Date : 2020-03-27 , DOI: 10.1007/s00011-020-01340-2
Sara Dahl 1 , Samuel Cerps 1 , Catarina Rippe 1 , Karl Swärd 1 , Lena Uller 1 , Daniel Svensson 1, 2 , Bengt-Olof Nilsson 1
Affiliation  

OBJECTIVE The importance of human host defense peptide LL-37 in vascular innate immunity is not understood. Here, we assess the impact of LL-37 on double-stranded RNA (dsRNA) signaling in human vascular smooth muscle cells. MATERIALS AND METHODS Cellular import of LL-37 and synthetic dsRNA (poly I:C) were investigated by immunocytochemistry and fluorescence imaging. Transcript and protein expression were determined by qPCR, ELISA and Western blot. Knockdown of TLR3 was performed by siRNA. RESULTS LL-37 was rapidly internalized, suggesting that it has intracellular actions. Co-stimulation with poly I:C and LL-37 enhanced pro-inflammatory IL-6 and MCP-1 transcripts several fold compared to treatment with poly I:C or LL-37 alone. Poly I:C increased IL-6 and MCP-1 protein production, and this effect was potentiated by LL-37. LL-37-induced stimulation of poly I:C signaling was not associated with enhanced import of poly I:C. Treatment with poly I:C and LL-37 in combination increased expression of dsRNA receptor TLR3 compared to stimulation with poly I:C or LL-37 alone. In TLR3 knockdown cells, treatment with poly I:C and LL-37 in combination had no effect on IL-6 and MCP-1 expression, showing loss of function. CONCLUSIONS LL-37 potentiates dsRNA-induced cytokine production through up-regulation of TLR3 expression representing a novel pro-inflammatory mechanism.

中文翻译:

人类宿主防御肽LL-37通过上调血管平滑肌细胞中TLR3的表达来促进双链RNA促炎信号转导。

目的还不清楚人类宿主防御肽LL-37在血管先天免疫中的重要性。在这里,我们评估LL-37对人血管平滑肌细胞中双链RNA(dsRNA)信号的影响。材料与方法通过免疫细胞化学和荧光成像研究了LL-37和合成dsRNA(poly I:C)的细胞导入。通过qPCR,ELISA和Western印迹测定转录物和蛋白质表达。通过siRNA敲低TLR3。结果LL-37被快速内在化,表明它具有细胞内作用。与单独使用poly I:C或LL-37的治疗相比,与poly I:C和LL-37的共刺激可增强促炎性IL-6和MCP-1转录本数倍。Poly I:C增加了IL-6和MCP-1蛋白的产生,而LL-37增强了这种作用。LL-37诱导的poly I:C信号传导刺激与poly I:C的增强进口无关。与单独用poly I:C或LL-37刺激相比,用poly I:C和LL-37联合治疗可提高dsRNA受体TLR3的表达。在TLR3敲低的细胞中,聚I:C和LL-37联合处理对IL-6和MCP-1表达无影响,显示功能丧失。结论LL-37通过上调代表新的促炎机制的TLR3表达来增强dsRNA诱导的细胞因子的产生。C和LL-37组合对IL-6和MCP-1表达没有影响,显示功能丧失。结论LL-37通过上调代表新的促炎机制的TLR3表达来增强dsRNA诱导的细胞因子的产生。C和LL-37组合对IL-6和MCP-1表达没有影响,显示功能丧失。结论LL-37通过上调代表新的促炎机制的TLR3表达来增强dsRNA诱导的细胞因子的产生。
更新日期:2020-03-27
down
wechat
bug