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Opposing roles of RNA receptors TLR3 and RIG-I in the inflammatory response to double-stranded RNA in a Kaposi's sarcoma cell line

机译:RNA受体TLR3和RIG-I在卡波济氏肉瘤细胞系对双链RNA的炎症反应中的相反作用

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Kaposi's sarcoma (KS) is strongly associated with KS herpes virus infection, and inflammation plays an important role in this disease. We have shown that human KS biopsy-derived SLK cells, which are of endothelial origin and form KS-like tumors in nude mice, express the viral RNA pattern recognition receptors Toll-like receptor 3 (TLR3), retinoic acid-inducible gene-I (XIG-1), and melanoma-differentiation-associated gene 5 (MDA5). Furthermore, SLK cells have enhanced release of IL-6, IL-8 (CXCL8), RANTES (CCL5), and IP-10 (CXCL 10) proteins in response to the synthetic viral RNA analog poly(l:C). SiRNA knockdowns demonstrated that TLR3 mediates this inflammatory response to poly(l:C) in SLK cells. Furthermore, knockdown of the RNA receptor RIG-I resulted in enhanced chemokine release, in a TLR3 pathway-dependent manner. Thus, exposure of KS cells to viral RNA ligands can result in a TLR3-mediated increase in the secretion of inflammatory proteins associated with KS cell growth that may contribute to disease. (C) 2007 Elsevier Inc. All rights reserved.
机译:卡波济肉瘤(KS)与KS疱疹病毒感染密切相关,炎症在该疾病中起重要作用。我们已经显示,人类KS活检来源的SLK细胞是内皮来源的,并在裸鼠中形成KS样肿瘤,它们表达病毒RNA模式识别受体Toll样受体3(TLR3),视黄酸诱导型基因I (XIG-1)和黑色素瘤分化相关基因5(MDA5)。此外,响应合成病毒RNA类似物poly(1:C),SLK细胞具有增强的IL-6,IL-8(CXCL8),RANTES(CCL5)和IP-10(CXCL 10)蛋白释放。 SiRNA敲低表明TLR3介导了SLK细胞中这种对poly(1:C)的炎症反应。此外,RNA受体RIG-I的敲低导致TLR3途径依赖性的趋化因子释放增强。因此,KS细胞暴露于病毒RNA配体会导致TLR3介导的与KS细胞生长相关的炎性蛋白质分泌增加,这可能会导致疾病。 (C)2007 Elsevier Inc.保留所有权利。

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