Involvement of NF-κB in changes of IFN-γ-induced CIITA/MHC-II and iNOS expression by influenza virus in macrophages

• Published in: Molecular immunology 2011-05, Vol.48 (9-10), p.1253-1262
• Main Authors: Hang, Do Thi Thu, Song, Jae-Young, Kim, Min-Young, Park, Jin-Woo, Shin, Yeun-Kyung
• Format: Article
• Language: English
• Subjects: Animals; Cell Line; CIITA/MHC-II; Gene Expression Regulation - drug effects; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - metabolism; IFN-γ; Influenza virus; iNOS; Interferon-gamma - pharmacology; Janus Kinases - metabolism; Macrophage Activation - drug effects; Macrophages; Macrophages - drug effects; Macrophages - enzymology; Macrophages - virology; Mice; NF-kappa B - metabolism; NF-κB; Nitric Oxide - secretion; Nitric Oxide Synthase Type II - metabolism; Nuclear Proteins - metabolism; Orthomyxoviridae - drug effects; Orthomyxoviridae - physiology; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - virology; Signal Transduction - drug effects; STAT1 Transcription Factor - metabolism; Trans-Activators - metabolism
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2011.03.010

Type II interferon (IFN-γ) plays an important role in defense against viral infection. Although this cytokine is found during influenza virus infection, it seems to have no protective function against the virus, and the reasons for this are not clear. To determine how the influenza virus overcomes the antiviral effects of IFN-γ, we examined the effect of A/Puerto-Rico/8/34 (H1N1) (PR8) infection on the expression of various IFN-γ inducible genes involved in defense against virus infection. The results showed that PR8 selectively affects IFN-γ induced MHC-II and iNOS expression in both the murine macrophage-like cell line, Raw264.7, and in primary alveolar macrophages. Infection of IFN-γ treated macrophages with PR8 resulted in decreased expression of CIITA/MHC-II and increased production of iNOS/NO. These changes correlate with activation of NF-κB but not with JAK/STAT signaling. The data indicate one possible mechanism underlying the ineffectiveness of IFN-γ against influenza virus, and suggest that NF-κB may be a promising target for anti-influenza drugs.