ISSN 1392-0146
ISSN 2029-0578 (online)
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2007 m. Nr. 3
Interferon-gamma does not restrict influenza virus
replication in RAW 264.7 and AMJ2-C11 macrophages
through the mechanism involving activation of inducible
nitric oxide synthase expression
Tomas KAČERGIUS, YUPING DENG, NORINE S. KUHN, Arvydas AMBROZAITIS, Stefan GRAVENSTEIN
Interferon-gamma (IFN-γ) antiviral activity operates partly via inducible nitric oxide synthase (iNOS) induction. Whether IFN-γ affects influenza A virus (IAV) replication within macrophages through this pathway is unknown. For the investigation, RAW 264.7 and AMJ2-C11 murine macrophages were exposed to IFN-γ, live IAV (A/PR/8/34) or their combination. At 24 h post-exposure, cell viability was evaluated by trypan blue dye exclusion, nitrite levels in macrophage culture supernatants were measured using the Griess reagent, and cells were harvested for reverse transcriptase (RT)-PCR. The IFN-γ-activated macrophages incubated with live IAV demonstrated a considerably greater cytopathic effect as well as a significant viability reduction than those without IAV, or with IAV minus IFN-γ (p < 0.05). Simultaneously, iNOS gene expression and nitric oxide (NO) production were increased in both cell lines. These findings indicate that IFN-γ-induced iNOS expression and NO synthesis and IFN-γ do not inhibit but permit at least partial IAV replication within macrophages.
Keywords: interferon-gamma, influenza virus, inducible nitric oxide synthase, nitric oxide, macrophages
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