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A synthetic single-stranded DNA, poly(dG,dC), induces interferon-alpha/beta and -gamma, augments natural killer
T Tokunaga1, S Yamamoto, K Namba
1Department of Cellular Immunology, National Institute of Health, Tokyo.
Abstract:
When various synthetic double- or single-stranded DNAs were incubated with spleen cells from mice (BALB/c or CDF1) at 37 degrees for 20 hr, it was found that some of the DNAs augmented NK activity and produced factors in the culture supernatants which showed antiviral activity and activity to render mouse macrophages cytotoxic toward tumor cells. Poly(dG,dC) showed the strongest activities, when incubated with spleen cells from lipopolysaccharide-nonresponsive mice, C3H/HeJ. The activity of the culture supernatant to activate macrophages was completely abolished by a small amount of anti-IFN gamma antibody. On the other hand, the virus-inhibitory activity of the supernatant was mostly neutralized by anti-IFN alpha/beta. When IMC tumor cells (5 x 10(5) cells) were mixed with poly(dG,dC) (100 micrograms) and then inoculated intradermally into CDF1 mice, the tumor did not take, while tumors grew progressively and killed the mice in a control group inoculated with tumor cells alone. Direct cytotoxicity of poly(dG,dC) at a concentration of 1,000 micrograms/ml against IMC cells was not observed in vitro.
Insights
Synthetic DNA, specifically poly(dG,dC), enhances immune cell activity, producing antiviral and anti-tumor effects. This DNA activates macrophages and inhibits tumor growth in mice, offering potential therapeutic applications.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- Synthetic nucleic acids can modulate immune responses.
- Spleen cells and macrophages are key components of the innate immune system.
- Interferons (IFNs) play crucial roles in antiviral and anti-tumor immunity.
Purpose of the Study:
- To investigate the immunomodulatory effects of various synthetic DNAs on mouse spleen cells.
- To identify specific synthetic DNAs that activate NK cell activity and macrophage cytotoxicity.
- To characterize the antiviral and anti-tumor properties of factors produced by stimulated immune cells.
Main Methods:
- Incubation of mouse spleen cells with synthetic double- and single-stranded DNAs.
- Assay of NK cell activity and macrophage cytotoxicity in culture supernatants.
- Neutralization studies using anti-IFN gamma and anti-IFN alpha/beta antibodies.
- In vivo tumor inoculation studies with synthetic DNA and tumor cells.
Main Results:
- Poly(dG,dC) significantly augmented NK activity and induced macrophage cytotoxicity.
- Culture supernatants exhibited antiviral activity and induced macrophage cytotoxicity.
- Macrophage activation was mediated by IFN-gamma, while antiviral activity involved IFN-alpha/beta.
- Intradermal inoculation of IMC tumor cells mixed with poly(dG,dC) prevented tumor take in mice.
Conclusions:
- Synthetic DNA, particularly poly(dG,dC), can activate innate immune cells to produce antiviral and anti-tumor factors.
- The study highlights the potential of synthetic DNA as an immunomodulatory agent for therapeutic applications.
- IFN-gamma and IFN-alpha/beta are key cytokines involved in the observed immune responses.