The molecular basis for the lack of immunostimulatory activity of vertebrate DNA.
نویسندگان
چکیده
Macrophages and B cells are activated by unmethylated CpG-containing sequences in bacterial DNA. The lack of activity of self DNA has generally been attributed to CpG suppression and methylation, although the role of methylation is in doubt. The frequency of CpG in the mouse genome is 12.5% of Escherichia coli, with unmethylated CpG occurring at approximately 3% the frequency of E. coli. This suppression of CpG alone is insufficient to explain the inactivity of self DNA; vertebrate DNA was inactive at 100 micro g/ml, 3000 times the concentration at which E. coli DNA activity was observed. We sought to resolve why self DNA does not activate macrophages. Known active CpG motifs occurred in the mouse genome at 18% of random occurrence, similar to general CpG suppression. To examine the contribution of methylation, genomic DNAs were PCR amplified. Removal of methylation from the mouse genome revealed activity that was 23-fold lower than E. coli DNA, although there is only a 7-fold lower frequency of known active CpG motifs in the mouse genome. This discrepancy may be explained by G-rich sequences such as GGAGGGG, which potently inhibited activation and are found in greater frequency in the mouse than the E. coli genome. In summary, general CpG suppression, CpG methylation, inhibitory motifs, and saturable DNA uptake combined to explain the inactivity of self DNA. The immunostimulatory activity of DNA is determined by the frequency of unmethylated stimulatory sequences within an individual DNA strand and the ratio of stimulatory to inhibitory sequences.
منابع مشابه
P-84: Characterization of Androgen Receptor Structure and Nucleocytoplasmic Shuttling of the Rice Field Eel
Background: Androgen receptor (AR) plays a critical role in prostate cancer and male sexual differentiation.Mechanisms by which AR acts and regulations of AR nucleocytoplasmic shuttling are not understood well. Materials and Methods: Degenerate PCR and RACE Cloning of AR Gene; Phylogenetic Analysis and Molecular Modeling;Real-time Fluorescent Quantitative RT-PCR; Northern Blot Hybridization;In ...
متن کاملMolecular detection of Leishmania infantum in road-killed carnivores from North of Iran, Golestan Province
Visceral leishmaniasis (VL) is an emerging zoonosis disease in countries of the Mediterranean basin caused by Leishmania infantum. Although domestic dogs are the main vertebrate hosts, many wild carnivores have been considered playing a role in the spreading of VL. Sporadic numbers of dog and human VL have been reported in Golestan Province in North Iran. The present study was performed to dete...
متن کاملIdentification of Phomopsis Species on Some Ornamental and Forest Plants in Iran on the Basis of the Morphological and Molecular
The Phomopsis is a genus of imperfect plant pathogenic fungus whose hosts comprise several species in different regions of the world, such as grapes, soybean, acacia, hollyhock, velvetleaf, and several other plants. In this study, samples collected from hollyhock, velvetleaf, purple bauhinia, and acacia plants suspected to be infected with Phomopsis fungi. Samples were culture...
متن کاملImmunostimulatory and growth-promoting potential of poly-β-hydroxybutyrate in rainbow trout (Oncorhynchus mykiss) fingerlings culture
In the current study, the effect of dietary supplementation of poly-β-hydroxybutyrate (PHB) on growth performance, digestive enzymes activity, body composition, non-specific immune response and diseases resistance of rainbow trout fingerlings were investigated. Five hundred and fifty-two healthy fingerlings (8.2±1.0 g) were randomly distributed in 12 tanks (150 L) at a density of 46 fish/ tank ...
متن کاملToll-like receptor 9: modulation of recognition and cytokine induction by novel synthetic CpG DNAs.
Bacterial and synthetic DNA containing unmethylated 2'-deoxyribo(cytidine-phosphate-guanosine) (CpG) dinucleotides in specific sequence contexts activate the vertebrate innate immune system. A molecular pattern recognition receptor, Toll-like receptor 9 (TLR9), recognizes CpG DNA and initiates the signalling cascade, although a direct interaction between CpG DNA and TLR9 has not been demonstrat...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Journal of immunology
دوره 170 7 شماره
صفحات -
تاریخ انتشار 2003