CpG RNA: identification of novel single-stranded RNA that stimulates human CD14+CD11c+ monocytes.

Download

index.pdf

Date

2005-02-15

Author

Sugiyama, T
Gürsel, Mayda
Takeshita, F
Coban, C
Conover, J
Kaisho, T
Akira, S
Klinman, DM
Ishii, KJ

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

264
views

134
downloads

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.

Subject Keywords

Immunology

URI

https://hdl.handle.net/11511/34938

Journal

Journal of immunology (Baltimore, Md. : 1950)

DOI

https://doi.org/10.4049/jimmunol.174.4.2273

Collections

Department of Biology, Article

Suggestions

OpenMETU
Core

CpG oligodeoxynucleotides protect normal and SIV-infected macaques from Leishmania infection. Verthelyi, D; Gürsel, Mayda; Kenney, RT; Lifson, JD; Liu, S; Mican, J; Klinman, DM (The American Association of Immunologists, 2003-05-01) Oligodeoxynucleotides containing CpG motifs (CpG ODNs) mimic microbial DNA and activate effectors of the innate immune response, which limits the spread of pathogens and promotes an adaptive immune response. CpG ODNs have been shown to protect mice from infection with intracellular pathogens. Unfortunately, CpG motifs that optimally stimulate humans are only weakly active in mice, mandating the use of nonhuman primates to monitor the activity and safety of "human" CpG ODNs in vivo. This study demonstrates t...
Cutting edge: Role of toll-like receptor 9 in CpG DNA-induced activation of human cells Takeshita, F; Leifer, CA; Gursel, I; Ishii, KJ; Takeshita, S; Gürsel, Mayda; Klinman, DM (The American Association of Immunologists, 2001-10-01) Unmethylated CpG motifs present in bacterial DNA stimulate a rapid and robust innate immune response. Human cell lines and PBMC that recognize CpG DNA express membrane-bound human Toll-like receptor 9 (hTLR9). Cells that are not responsive to CpG DNA become responsive when transfected with hTLR9. Expression of hTLR9 dramatically increases uptake of CpG (but not control) DNA into endocytic vesicles. Upon cell stimulation, hTLR9 and CpG DNA are found in the same endocytic vesicles. Cells expressing hTLR9 are ...
Repetitive elements in mammalian telomeres suppress bacterial DNA-induced immune activation. Gursel, I; Gürsel, Mayda; Yamada, H; Ishii, KJ; Takeshita, F; Klinman, DM (The American Association of Immunologists, 2003-08-01) Bacterial DNA contains immunostimulatory CpG motifs that trigger an innate immune response capable of promoting host survival following infectious challenge. Yet CpG-driven immune activation may also have deleterious consequences, ranging from autoimmune disease to death. We find that repetitive elements present at high frequency in mammalian telomeres, but rare in bacteria, down-regulate CpG-induced immune activation. Suppressive activity correlates with the ability of telomeric TTAGGG repeats to form G-te...
Plasmacytoid Dendritic Cell Response to CpG ODN Correlates with CXCL16 Expression and Is Inhibited by ox-LDL Gürsel, Mayda; GÜRSEL, İHSAN (Hindawi Limited, 2013-01-01) Structurally distinct classes of synthetic CpG oligonucleotides (ODN) differentially activate human immune cells. K-type ODN trigger plasmacytoid dendritic cells (pDCs) to differentiate and produce TNF alpha. In contrast, D-type ODN stimulate large amounts of IFN alpha secretion from pDCs. The cell-surface receptor CXCL16 was previously shown to influence the nature and specificity of CpG ODN-induced immune activation. Here, we evaluated the expression and function of CXCL16 on pDC from healthy volunteers. ...
Rapid differentiation of MSC into adipocytes and osteocytes is facilitated by Toll-Like receptor engagement Tas, Ibrahim; Tokcaer-Keskin, Zeynep; Ayhan, Fatma; Gürsel, Mayda; Akcali, Kamil (2010-04-01) Mesenchymal stem cells are multipotent progenitor cells capable of differentiating into several lineages including adipocytes, and osteocytes. While they are regarded as non-immunogenic, accumulating evidence suggests that MSC expresses several TLRs. We checked the contribution of TLR ligands to MSC differentiation. Rat bone marrow derived MSC surface marker and TLR transcript levels were checked by FACS and RT-PCR respectively. MSCs were CD29hi, CD71dim, CD90hi, and negative for CD45 & CD34. They expressed...

Citation Formats

T. Sugiyama et al., “CpG RNA: identification of novel single-stranded RNA that stimulates human CD14+CD11c+ monocytes.,” Journal of immunology (Baltimore, Md. : 1950), pp. 2273–9, 2005, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/34938.