HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) A correction has been published Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sugiyama, T. Articles by Ishii, K. J. Search for Related Content PubMed PubMed Citation Articles by Sugiyama, T. Articles by Ishii, K. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH

CpG RNA: Identification of Novel Single-Stranded RNA That Stimulates Human CD14⁺CD11c⁺ Monocytes

Takahiro Sugiyama^*,, Mayda Gursel^*, Fumihiko Takeshita, Cevayir Coban^,¶, Jacqueline Conover^*, Tsuneyasu Kaisho, Shizuo Akira^,¶, Dennis M. Klinman^* and Ken J. Ishii^1,*,,¶

^* Section of Retroviral Immunology, Division of Viral Products, Center for Biologics, Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892; Laboratory for Host Defense, RIKEN Research Center for Allergy and Immunology, Yokahama, Japan; Department of Molecular Biodefense Research, School of Medicine, Yokohama City University, Yokohama, Japan; Exploratory Research for Advanced Technology, Japan Science and Technology Agency, Osaka University, Osaka, Japan; and ^¶ Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan

Synthetic immunostimulatory nucleic acids such as CpG DNA are being harnessed therapeutically as vaccine adjuvants, anticancer or antiallergic agents. Efforts to identify nucleic acid-based agents capable of more specifically modulating the immune system are being developed. The current study identifies a novel class of single-stranded oligoribonucleotides (ORN) containing unmethylated CpG motifs and a poly(G) run at the 3' end (CpG ORN) that directly stimulate human CD14⁺CD11c⁺ monocytes but not dendritic cells or B cells. CpG ORN activate NF-B and p38 MAPK, resulting in IL-6 and IL-12 production and costimulatory molecule up-regulation but not IFN. Methylation of cytosine at the 5' portion in core CpG motif abrogates such activation. TLR3, 7, 8, or 9 alone did not confer response to CpG ORN, in contrast to previously reported respective nucleic acid ligands. These data suggest that CpG ORN represent a novel class of synthetic immunostimulatory nucleic acids with distinct target cells, receptors, and functions from that of previously known immunomodulatory nucleic acids.

This article has been cited by other articles:

				M. M. Petzke, A. Brooks, M. A. Krupna, D. Mordue, and I. Schwartz Recognition of Borrelia burgdorferi, the Lyme Disease Spirochete, by TLR7 and TLR9 Induces a Type I IFN Response by Human Immune Cells J. Immunol., October 15, 2009; 183(8): 5279 - 5292. [Abstract] [Full Text] [PDF]

				C. C. Burns, R. Campagnoli, J. Shaw, A. Vincent, J. Jorba, and O. Kew Genetic Inactivation of Poliovirus Infectivity by Increasing the Frequencies of CpG and UpA Dinucleotides within and across Synonymous Capsid Region Codons J. Virol., October 1, 2009; 83(19): 9957 - 9969. [Abstract] [Full Text] [PDF]

				A. Ablasser, H. Poeck, D. Anz, M. Berger, M. Schlee, S. Kim, C. Bourquin, N. Goutagny, Z. Jiang, K. A. Fitzgerald, et al. Selection of Molecular Structure and Delivery of RNA Oligonucleotides to Activate TLR7 versus TLR8 and to Induce High Amounts of IL-12p70 in Primary Human Monocytes J. Immunol., June 1, 2009; 182(11): 6824 - 6833. [Abstract] [Full Text] [PDF]

				Z. Wang, L. Xiang, J. Shao, and Z. Yuan The 3' CCACCA Sequence of tRNAAla(UGC) Is the Motif That Is Important in Inducing Th1-Like Immune Response, and This Motif Can Be Recognized by Toll-Like Receptor 3. Clin. Vaccine Immunol., July 1, 2006; 13(7): 733 - 739. [Abstract] [Full Text] [PDF]