Poly (I:C), a synthetic double-stranded RNA (dsRNA) analog, is an immunostimulant that acts as the most potent interferon (IFN) inducer. Toll-like receptor- 3 (TLR3) agonist[1].
Poly (I:C) suppressed cytopathic effects (CPE) induced by CHIKV infection in BEAS-2B cells in the presence of Poly (I:C) and inhibited the replication of CHIKV in the cells. Both Poly (I:C) and CHIKV infection upregulate the expression of TLR3 in BEAS-2B cells[1].DsRNA poly(I:C) up-regulated the expression of IFNβ and apoptosis-associated genes in cervical cancer cells, activating both intrinsic and extrinsic apoptotic pathways, and eventually inducing cell death[8].Stable maturation of DC can be simply induced by the addition of polyriboinosinic polyribocytidylic acid (poly(I:C))[3].Poly(I:C) decreased the rate of successful in vitro fertilization via DNA damage and abnormal spindle morphology at the first cleavage and inhibited early embryonic development by inducing immune response and promoting blastocyst cell apoptosis[9]. Mixtures that included the TLR7/8 agonists R848 or CL075, combined with the Poly (I:C), yield 3-d mature dendritic cells [2].
Poly(I:C)-activated macrophages displayed enhanced phagocytosis after CD47 blockade. Compared with mice receiving monotherapy, those received Poly(I:C) in combination with anti-CD47 mAb exhibited significantly inhibited tumor growth[4]. In vivo, poly(I:C) enhanced cell surface expression of Mac-1 on neutrophils in mice and facilitated their infiltration to lung tissues. Poly(I:C) also downregulated thrombomodulin expression in mouse tissues and reduced its circulating soluble level in plasma[5].1.25 and 5 mg/kg poly(I:C) preconditioning significantly reduced myocardial infarct size and cardiac dysfunction. Moreover, poly(I:C) significantly promoted cell survival by restoring autophagy flux and then regulating it to an adequate level Increased autophagy protein Beclin1 and LC3II together with p62 degradation after additional chloroquine[6].In mice,following Poly I:C exposure, a significant decrease in DA-D2 receptor binding, reduction in corpus callosum calibre and MOG immunolabelling indicating demyelination and a significant decrease in locomotor activity, neuromuscular strength and motor coordination signify motor deficits and hypokinetic influence of early life viral infection[7].
聚(I:C)是一种合成的双链RNA类似物，是一种免疫刺激剂，可作为最强效的干扰素（IFN）诱导剂。它是Toll样受体-3（TLR3）激动剂[1]。
在存在Poly(I:C)的情况下，Poly(I:C)抑制了CHIKV感染引起的BEAS-2B细胞细胞病变效应(CPE)，并抑制了病毒在细胞中的复制。Poly(I:C)和CHIKV感染都上调了BEAS-2B细胞中TLR3的表达[1]。DsRNA poly(I:C)上调了宫颈癌细胞中IFNβ和与凋亡相关基因的表达，激活内源性和外源性凋亡途径，并最终诱导细胞死亡[8]。通过添加聚核苷酸聚核苷酸酰化肽(poly(I:C))可以简单地诱导DC稳定成熟[3]。Poly(I:C)通过引发免疫反应和促进囊胚细胞凋亡，在第一次分裂时降低体外受精成功率并抑制早期胚胎发育[9]。包含TLR7/8激动剂R848或CL075以及Poly (I: C)混合物可产生3天成熟树突状细胞 [2]。
在CD47阻断后，聚(I:C)激活的巨噬细胞表现出增强的吞噬作用。与单一治疗组相比，接受Poly(I:C)和抗CD47 mAb联合治疗的小鼠明显抑制了肿瘤生长[4]。在体内，Poly(I:C)增强了小鼠中中性粒细胞上Mac-1的细胞表面表达，并促进它们浸润到肺组织中。Poly(I:C)还下调了小鼠组织中凝血调节蛋白原模因素(thrombomodulin)的表达，并降低其循环可溶性水平[5]。1.25和5 mg/kg Poly(I:C)预处理显著减少心肌梗死面积和心功能障碍。此外，Poly(I:C)通过恢复自噬通路并将其调节到适当水平来显著促进细胞存活，在额外使用氯喹后增加自噬蛋白Beclin1和LC3II以及p62降解[6]。在小鼠身上，在经历聚I：C暴露后，DA-D2受体结合量显着降低、胼胝体直径缩小、MOG免疫标记表明脱髓鞘，以及运动活动度、神经肌肉力量和运动协调性显着降低，这表明早期病毒感染对运动功能的影响[7]。
参考文献:
[1]: Li YG, Siripanyaphinyo U, et,al. Poly (I:C), an agonist of toll-like receptor-3, inhibits replication of the Chikungunya virus in BEAS-2B cells. Virol J. 2012 Jun 14;9:114. doi: 10.1186/1743-422X-9-114. PMID: 22698190; PMCID: PMC3490739.
[2]: Spranger S, Javorovic M, et,al. Generation of Th1-polarizing dendritic cells using the TLR7/8 agonist CL075. J Immunol. 2010 Jul 1;185(1):738-47. doi: 10.4049/jimmunol.1000060. Epub 2010 May 28. PMID: 20511554.
[3]: Verdijk RM, Mutis T, et,al. Polyriboinosinic polyribocytidylic acid (poly(I:C)) induces stable maturation of functionally active human dendritic cells. J Immunol. 1999 Jul 1;163(1):57-61. PMID: 10384099.
[4]: Zhong C, Wang L, et,al. Poly(I:C) enhances the efficacy of phagocytosis checkpoint blockade immunotherapy by inducing IL-6 production. J Leukoc Biol. 2021 Dec;110(6):1197-1208. doi: 10.1002/JLB.5MA0421-013R. Epub 2021 May 14. PMID: 33988261.
[5]: Cai X, Panicker SR, et,al.Protective Role of Activated Protein C against Viral Mimetic Poly(I:C)-Induced Inflammation. Thromb Haemost. 2021 Nov;121(11):1448-1463. doi: 10.1055/s-0041-1726093. Epub 2021 Mar 11. PMID: 33706396; PMCID: PMC8433266.
[6]: Chen E, Chang H, et,al. Poly(I:C) attenuates myocardial ischemia/reperfusion injury by restoring autophagic function. FASEB J. 2022 May;36(5):e22317. doi: 10.1096/fj.202101220RR. PMID: 35438806.
[7]:Singh B, Dhuriya YK, et,al. Early life exposure to poly I:C impairs striatal DA-D2 receptor binding, myelination and associated behavioural abilities in rats. J Chem Neuroanat. 2021 Dec;118:102035. doi: 10.1016/j.jchemneu.2021.102035. Epub 2021 Sep 28. PMID: 34597812.
[8]: Meng X, Cui X, et,al. poly(I:C) synergizes with proteasome inhibitors to induce apoptosis in cervical cancer cells. Transl Oncol. 2022 Apr;18:101362. doi: 10.1016/j.tranon.2022.101362. Epub 2022 Feb 9. PMID: 35151092; PMCID: PMC8842080.
[9]: Wang Z, Chen S, et,al. Poly(I:C) exposure during in vitro fertilization disrupts first cleavage of mouse embryos and subsequent blastocyst development. J Reprod Immunol. 2022 Jun;151:103635. doi: 10.1016/j.jri.2022.103635. Epub 2022 Apr 30. PMID: 35525084.
| Cell experiment [1]: | |
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Cell lines |
BEAS-2B cells |
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Preparation Method |
BEAS-2B cells were seeded in 6-well plates one day before Poly (I:C) treatment. One hour before infection at multiplicity of infection (MOI) 0.01, 1, or 5, the cells were pre-treated with 4 μg/ml of Poly (I:C) or left untreated. After adsorption, the cells were maintained in the medium with or without Poly (I: C) (4 μg/ml). The CPE was observed at 24, 48, and 72 h postinfection (p.i.) under a microscope. |
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Reaction Conditions |
4 μg/ml Poly (I: C) for 24/48/72 h |
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Applications |
Poly (I:C) suppressed cytopathic effects (CPE) induced by CHIKV infection in BEAS-2B cells in the presence of Poly (I:C) and inhibited the replication of CHIKV in the cells. The virus titers of Poly (I:C)-treated cells were much lower compared with those of untreated cells. CHIKV infection and Poly (I:C) treatment of BEAS-2B cells induced the production of IFN-β and increased the expression of anti-viral genes, including IFN-α, IFN-β, MxA, and OAS. Both Poly (I:C) and CHIKV infection upregulate the expression of TLR3 in BEAS-2B cells. |
| Animal experiment [2]: | |
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Animal models |
C57BL/6J mouse |
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Preparation Method |
Injection of MC38 cells into C57BL/6J mice and the subsequent intraperitoneal injections of Poly(I:C),Mice were treated with 50 μg Poly(I:C) by intraperitoneal injection on days 8, 11, 14, 17, 20 and 23. |
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Dosage form |
50 μg Poly(I:C) by intraperitoneal injection on days 8, 11, 14, 17, 20 and 23. |
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Applications |
Poly(I:C)-activated macrophages displayed enhanced phagocytosis after CD47 blockade. Compared with mice receiving monotherapy, those received Poly(I:C) in combination with anti-CD47 mAb exhibited significantly inhibited tumor growth. Moreover, in vivo delivery of Poly(I:C) plus anti-CD47 mAb to tumor-bearing mice altered the tumor immune microenvironment. |
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参考文献: [1]: Li YG, Siripanyaphinyo U, et,al. Poly (I:C), an agonist of toll-like receptor-3, inhibits replication of the Chikungunya virus in BEAS-2B cells. Virol J. 2012 Jun 14;9:114. doi: 10.1186/1743-422X-9-114. PMID: 22698190; PMCID: PMC3490739. |
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