相反的作用的RNA 受体 TLR3和RIG-I在炎症反应中双链RNA在一个卡波济氏肉瘤细胞系原创性研究文章.pdf

Available online at Cellular Immunology 249 (2007) 55–62 /locate/ycimm Opposing roles of RNA receptors TLR3 and RIG-I in the inflammatory response to double-stranded RNA in a Kaposi’s sarcoma cell line April J. Livengood *, Christina C.N. Wu, Dennis A. Carson Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093-0820, USA Received 6 September 2007; accepted 10 November 2007 Available online 26 December 2007 Abstract 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 (RIG-I), and melanoma-differ- entiation-associated gene 5 (MDA5). Furthermore, SLK cells have enhanced release of IL-6, IL-8 (CXCL8), RANTES (CCL5), and IP- 10 (CXCL10) proteins in response to the synthetic viral RNA analog poly(I:C). SiRNA knockdowns demonstrated that TLR3 mediates this inflammatory response to poly(I:C) in SLK cells. Furthermore, knockdown of the RNA receptor RIG-I resulted in enhanced che- mokine 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. 2007 Elsevier Inc. All rights reserved. Keywords: