IL-15 induces IFN-β and iNOS gene expression, and antiviral activity of murine macrophage RAW 264.7 cells

• Published in: Immunology letters 2004-02, Vol.91 (2-3), p.171-178
• Main Authors: Liu, Ge, Zhai, Qingzhu, Schaffner, Dustin, Bradburne, Chris, Wu, Aiguo, Hayford, Alice, Popov, Serguei, Grene, Edith, Bailey, Charlie, Alibek, Ken
• Format: Article
• Language: English
• Subjects: Animals; Bystander Effect - drug effects; Cell Line; Gene Expression Regulation - drug effects; Humans; IFN-β; IL-15; iNOS; Interferon-beta - analysis; Interferon-beta - antagonists & inhibitors; Interferon-beta - genetics; Interferon-beta - immunology; Interferon-gamma - analysis; Interferon-gamma - genetics; Interferon-gamma - pharmacology; Interleukin-15 - pharmacology; Macrophages - drug effects; Macrophages - enzymology; Macrophages - immunology; Macrophages - metabolism; Mice; Murine macrophage cells; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase Type II; Nitrogen Oxides - metabolism; omega-N-Methylarginine - pharmacology; Poxviruses; RNA, Messenger - genetics; RNA, Messenger - metabolism; Transcription, Genetic - drug effects; Tumor Necrosis Factor-alpha - metabolism; Vaccinia virus; Vaccinia virus - immunology; Vaccinia virus - physiology; Virus Replication - drug effects
• ISSN: 0165-2478; 1879-0542
• DOI: 10.1016/j.imlet.2003.11.015

The effects of interleukine-15 (IL-15) on macrophage activation and antiviral activity have been investigated in this study. We have provided evidence that IL-15 stimulates murine macrophage RAW 264.7 cells to release nitric oxide (NO) and inhibit vaccinia virus (VV) replication in bystander human 293 cells in a dose-dependent manner. The IL-15-induced antiviral activity was partially mediated by NO, as blocking NO production by NO synthase (iNOS) inhibitor NG-monomethyl-L-arginine acetate (L-NMA) partially restored the virus replication. Interferon-γ (IFN-γ) was not detectable by ELISA in the cell supernatant of IL-15-activated macrophages or in the co-cultures of macrophages and infected bystander cells. Neutralizing anti-IFN-γ, anti-IFN-γ receptor R2, anti-TNF-α, or anti-IL-12 antibodies had no effect on NO production or antiviral activity. In contrast, neutralizing anti-IFN-α/β antibody completely restored the VV replication and reduced the NO level to one third of that in the control. Elevated mRNA levels of IFN-β and iNOS genes were detected in IL-15-activated RAW 264.7 cells by RT-PCR. Our data suggest that IL-15 is capable of inducing IFN-β, which could participate in NO-mediated antiviral effect.