IL-15 induces IFN-beta and iNOS gene expression, and antiviral activity of murine macrophage RAW 264.7 cells.
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-gamma (IFN-gamma) 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-gamma, anti-IFN-gamma receptor R2, anti-TNF-alpha, or anti-IL-12 antibodies had no effect on NO production or antiviral activity. In contrast, neutralizing anti-IFN-alpha/beta antibody completely restored the VV replication and reduced the NO level to one third of that in the control. Elevated mRNA levels of IFN-beta 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-beta, which could participate in NO-mediated antiviral effect.
Liu
Ge
G
Advanced Biosystems Inc., George Mason University, 10900 University Boulevard, MSN 1A8, Manassas, VA 20110, USA. ge.liu@analex.com
Zhai
Qingzhu
Q
Schaffner
Dustin
D
Bradburne
Chris
C
Wu
Aiguo
A
Hayford
Alice
A
Popov
Serguei
S
Grene
Edith
E
Bailey
Charlie
C
Alibek
Ken
K
D000818:Animals; D024201:Bystander Effect / Q000187:drug effects; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D016899:Interferon-beta / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D007371:Interferon-gamma / Q000032:analysis / Q000235:genetics / Q000494:pharmacology; D019409:Interleukin-15 / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D009589:Nitrogen Oxides / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014616:Vaccinia virus / Q000276:immunology / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology
D019409:Interleukin-15; D009589:Nitrogen Oxides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D016899:Interferon-beta; D007371:Interferon-gamma; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse