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Requirements for effective inhibition of immunostimulatory CpG motifs by neutralizing motifs.
Zhao, H; Cheng, S H; Yew, N S.
Afiliação
  • Zhao H; Genzyme Corporation, Framingham, MA 01701-9322, USA.
Antisense Nucleic Acid Drug Dev ; 10(5): 381-9, 2000 Oct.
Article em En | MEDLINE | ID: mdl-11079577
The DNA of bacteria and many viruses contain unmethylated CpG dinucleotides in particular sequence contexts that activate vertebrate immune cells. A subset of these CpG motifs was previously found to oppose the effects of immunostimulatory (CpG-S) motifs and has been termed neutralizing (CpG-N) motifs. Here we show that oligodeoxynucleotides (ODNs) composed of clusters of CpG-N motifs could partially inhibit the induction of interleukin-12 (IK-12) from mouse spleen cells by ODN containing CpG-S motifs. However, non-CpG-containing ODN were also inhibitory, suggesting that neutralization of CpG-S ODNs by CpG-N ODNs in trans was nonspecific. Neutralization of CpG-S motifs by CpG-N motifs in cis was specific, but the degree of inhibition was strongly dependent on the particular CpG-S motif being neutralized, with motifs having an A residue 5' to the CG being much more resistant to inhibition than motifs having a T residue 5' to the CG. The degree of inhibition was dependent on the spacing between the CpG-S and CpG-N motifs, with the ability to neutralize inversely correlating with distance. In addition, whereas ODNs containing extended clusters of CpG-N motifs were nonstimulatory, isolated CpG-N motifs remained stimulatory in most sequence contexts. Finally, CpG-N ODNs were shown to be nonstimulatory when instilled into the lungs of BALB/c mice, but the ability of CpG-N motifs to neutralize CpG-S motifs in cis was not observed. These results show that there are precise and fairly complex interactions between immunostimulatory and inhibitory sequence motifs that govern whether a given DNA is able to activate the vertebrate immune system.
Assuntos
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Base de dados: MEDLINE Assunto principal: Oligodesoxirribonucleotídeos / Adjuvantes Imunológicos / Ilhas de CpG Limite: Animals Idioma: En Revista: Antisense Nucleic Acid Drug Dev Assunto da revista: BIOLOGIA MOLECULAR / BIOQUIMICA / FARMACOLOGIA Ano de publicação: 2000 Tipo de documento: Article País de afiliação: Estados Unidos
Buscar no Google
Base de dados: MEDLINE Assunto principal: Oligodesoxirribonucleotídeos / Adjuvantes Imunológicos / Ilhas de CpG Limite: Animals Idioma: En Revista: Antisense Nucleic Acid Drug Dev Assunto da revista: BIOLOGIA MOLECULAR / BIOQUIMICA / FARMACOLOGIA Ano de publicação: 2000 Tipo de documento: Article País de afiliação: Estados Unidos