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Medical Research Service, Durham Veterans Administration Hospital and Division of Rheumatology, Allergy and Clinical Immunology, Department of Medicine, Duke University Medical Center, Durham, North Carolina
Correspondence: Dr. David S. Pisetsky, Durham VA Medical Center, Box 151G, 508 Fulton Street, Durham, NC 27705. E-mail: dpiset{at}acpub.duke.edu
Synthetic 30-mer phosphorothioate (Ps) oligonucleotides (ODN) comprised of single bases (SdA30, SdC30, SdG30, and SdT30) were assessed for their effects on nitric oxide (NO) production by murine bone marrow macrophages (BMMC) and macrophage cell lines J774 and RAW264.7. Pretreatment of these cells with any of the four Ps ODN inhibited NO production induced by CpG ODN, E. coli DNA (EC DNA), or LPS. This inhibition was time- and dose-dependent and was observed even if the Ps ODN were added as long as 12 h after stimulation. As in the case of stimulatory ODN, inhibition was dependent on backbone structure and length. Thus, all four 30-mer, single-base Ps ODN were inhibitory, and only dG30 among phosphodiester ODN was inhibitory. Together, these observations indicate that Ps ODN can inhibit macrophage production of inflammatory mediators, suggesting a role of these compounds as immunomodulatory agents.
Key Words: DNA • CpG • lipopolysaccharide • inflammatory mediator
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