Identification of methylated CpG motifs as inhibitors of the immune stimulatory CpG motifs

Y CHEN; P LENERT; R WEERATNA; M MCCLUSKIE; T WU; H. L DAVIS; A. M KRIEG

doi:10.1038/sj.gt.3301482

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Identification of methylated CpG motifs as inhibitors of the immune stimulatory CpG motifs

Journal article

Peer reviewed

Identification of methylated CpG motifs as inhibitors of the immune stimulatory CpG motifs

Y CHEN, P LENERT, R WEERATNA, M MCCLUSKIE, T WU, H. L DAVIS and A. M KRIEG

Gene therapy, Vol.8(13), pp.1024-1032

2001

DOI: 10.1038/sj.gt.3301482

PMID: 11438837

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Abstract

The unmethylated CpG motifs within E. coli DNA (EC) cause immune stimulation. In contrast, mammalian DNA such as calf thymus (CT) DNA had been thought to be immunologically inert. In this article, we demonstrate that CT DNA unexpectedly specifically inhibits the immune activation by EC but not that by endotoxin. This inhibitory effect was mediated in the signaling pathway activated by EC since CT DNA markedly inhibited the CpG-induced nuclear translocation of the transcription factors, NF-κB and AP-1. In addition, CT DNA significantly inhibited the synergistic immune activation by EC and endotoxin. The mechanism of the inhibition by CT DNA probably did not involve the inhibition of the cellular uptake of EC. Using a CpG-depleted plasmid, we demonstrated that CpG methylation played an important role in the inhibition by CT DNA. Compared with unmethylated plasmid DNA, CpG-methylated DNA inhibited the immune activation by EC to the same extent as did CT DNA. Importantly, the inhibitory effect of CT DNA was also observed in vivo. Our results suggest that methylated DNA may be applied to alleviate the unwanted immune stimulation and inflammation in systemic inflammatory response syndrome and in gene therapy with plasmid DNA.

Biotechnology

Gene Therapy

Fundamental and applied biological sciences. Psychology

Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy

Health. Pharmaceutical industry

Industrial applications and implications. Economical aspects

Transfusions. Complications. Transfusion reactions. Cell and gene therapy

Applied cell therapy and gene therapy

Biological and medical sciences

Medical sciences

Details

Title: Subtitle: Identification of methylated CpG motifs as inhibitors of the immune stimulatory CpG motifs
Creators: Y CHEN - Department of Internal Medicine, University of Iowa, Iowa City, IA, United States
P LENERT - Department of Internal Medicine, University of Iowa, Iowa City, IA, United States
R WEERATNA - Loeb Health Research Institute at the Ottawa Hospital, Offawa, Canada
M MCCLUSKIE - Loeb Health Research Institute at the Ottawa Hospital, Offawa, Canada
T WU - Ottawa Hospital Research Institute
H. L DAVIS - Loeb Health Research Institute at the Ottawa Hospital, Offawa, Canada
A. M KRIEG - Department of Internal Medicine, University of Iowa, Iowa City, IA, United States
Resource Type: Journal article
Publication Details: Gene therapy, Vol.8(13), pp.1024-1032
DOI: 10.1038/sj.gt.3301482
PMID: 11438837
NLM abbreviation: Gene Ther
ISSN: 0969-7128
eISSN: 1476-5462
Publisher: Nature Publishing Group
Language: English
Date published: 2001
Academic Unit: Immunology; Internal Medicine
Record Identifier: 9984094727002771

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