Anti-proliferative effects of phosphodiester oligodeoxynucleotides.
The immunostimulatory effects of cytosine-phosphate-guanosine (CpG)-containing oligodeoxynucleotides (ODNs) have been extensively documented. In this paper, we describe the inhibitory effects of ODNs that contain natural phosphodiester backbones (O-ODNs) on the immunostimulation caused by CpG-containing phosphorothioated ODNs (CpG-S). CpG-S stimulation of mouse splenocyte proliferation was reduced by the addition of O-ODNs that contained or lacked the CpG-motif (CpG-containing phosphodiester oligodeoxynucleotide, CpG-O or GpC-O). The total number of cultured splenocytes was up-regulated by CpG-S, whereas repetitive addition of O-ODNs to the cell cultures inhibited this effect. The frequency of T2-like B cells was found to be increased by CpG-S. The culture supernatants of CpG-S-treated splenocytes contained elevated levels of IL-10 and IL-6. However, IL-10 and IL-6 production was down-regulated significantly by the combination of CpG-S and either CpG-O or GpC-O. The O-ODN mediated inhibition of proliferation was less pronounced in IL-10-/- mice. Thus, the O-ODNs, irrespective of CpG content, exerted inhibitory activities on the proliferation of B cells. These anti-proliferative effects appear to be mediated both by the down-regulation of IL-10 production and increased apoptosis.
Bjersing
Jan L
JL
Department of Rheumatology and Inflammation Research, University of Göteborg, Guldhetsgatan IOA, Göteborg 413 46, Sweden. jan.bjersing@rheuma.gu.se
Tarkowski
Andrej
A
Collins
L Vincent
LV
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003850:Deoxyribonuclease I / Q000172:deficiency / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D016328:NF-kappa B / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology; D013873:Thionucleotides / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D015850:Interleukin-6; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D013873:Thionucleotides; D016753:Interleukin-10; D003850:Deoxyribonuclease I