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Polyinosinic-polycytidylic acid是一种TLR3激动剂

Polyinosinic-polycytidylic acid (Poly(I:C)) 是双链 RNA 的合成类似物,是一种 TLR3 和视黄酸诱导型基因 I 受体 (RIG-I 和 MDA5) 的激动剂。Polyinosinic-polycytidylic acid 可以用作疫苗佐剂,以增强先天性和适应性免疫反应,并改变肿瘤的微环境,还可以直接触发癌细胞发生凋亡 (apoptosis)。
 
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体外研究:
Polyinosinic-polycytidylic acid (0.5-5 μg/mL, 3-24 h) 呈现剂量和时间依赖性增加诱导永生化气道上皮细胞的细胞旁通透性[4]。
Polyinosinic-polycytidylic acid (5 μg/mL, 24 h) 对 16HBE14o- 细胞没有细胞毒性[4]。
Polyinosinic-polycytidylic acid (5 μg/mL, 6 h) 在 16HBE14o- 细胞中诱导上皮顶端连接复合体和紧密连接的破坏[4]。
 
 
体内研究:
Polyinosinic-polycytidylic acid (2.5-10 mg/mL, Stereotaxic injection, single dose) 在脑黑质和背外侧纹状体中诱导持续的炎症反应[2]。
Polyinosinic-polycytidylic acid (10 μg/mouse, Intraperitoneal injection, single dose) 降低小鼠的肺肿瘤生长[3]。
Polyinosinic-polycytidylic acid (1.25 mg/kg, Intraperitoneal injection, single dose) 在 MCAO 模型小鼠中通过 TLR3 下调TLR4/MyD88 信号通路发挥脑缺血再灌注损伤的治疗作用[5]。
 
 
参考文献
[1]. Cheng Y, Xu F. Anticancer function of polyinosinic-polycytidylic acid [J]. Cancer biology & therapy, 2010, 10(12): 1219-1223.  
[2]. Deleidi M, Hallett P J, Koprich J B, et al. The Toll-like receptor-3 agonist polyinosinic: polycytidylic acid triggers nigrostriatal dopaminergic degeneration [J]. Journal of Neuroscience, 2010, 30(48): 16091-16101.  
[3]. Forte G, Rega A, Morello S, et al. Polyinosinic-polycytidylic acid limits tumor outgrowth in a mouse model of metastatic lung cancer [J]. The Journal of Immunology, 2012, 188(11): 5357-5364.  
[4]. Rezaee F, Meednu N, Emo J A, et al. Polyinosinic: polycytidylic acid induces protein kinase D–dependent disassembly of apical junctions and barrier dysfunction in airway epithelial cells [J]. Journal of Allergy and Clinical Immunology, 2011, 128(6): 1216-1224. e11.  
[5]. Wang P F, Fang H, Chen J, et al. Polyinosinic-polycytidylic acid has therapeutic effects against cerebral ischemia/reperfusion injury through the downregulation of TLR4 signaling via TLR3 [J]. The Journal of Immunology, 2014, 192(10): 4783-4794.  
[6]. Alexopoulou L, Holt AC, Medzhitov R, Flavell RA. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature. 2001;413(6857):732-738.  
[7]. Matsumoto M, Kikkawa S, Kohase M, Miyake K, Seya T. Establishment of a monoclonal antibody against human Toll-like receptor 3 that blocks double-stranded RNA-mediated signaling. Biochem Biophys Res Commun. 2002;293(5):1364-1369.

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