caa a22 4500 475766504 CHVBK 20180406123607.0 cr unu---uuuuu 170329e20000301xx s 000 0 eng 10.1007/s007050050048 doi (NATIONALLICENCE)springer-10.1007/s007050050048 Herpes simplex virus type 2 infection of macrophages impairs IL-4-mediated inhibition of NO production through TNF-α-induced activation of NF-κB [Elektronische Daten] [S. R. Paludan, S. Ellermann-Eriksen, L. Malmgaard, S. C. Mogensen] Summary.:  Nitric oxide (NO) production in macrophages by the interferon (IFN)-γ-inducible NO synthase has been shown to play a role in clearance of viral infections. We have previously shown that IFN-γ-induced NO production is augmented by herpes simplex virus type 2 (HSV-2) infection through autocrine tumour necrosis factor (TNF)-α secretion and is inhibited by interleukin (IL)-4. Here we investigated the effect of HSV-2 infection on the inhibitory function of IL-4. Virus infection of mouse J774A.1 macrophages strongly reduced the ability of IL-4 to inhibit IFN-γ-induced NO production, even at very high IL-4 concentrations. The effect of HSV-2 infection did not involve the IL-4 signal transduction pathway through STAT6. IL-4 reduced virus-induced TNF-α secretion and nuclear factor (NF)-κB activation significantly, but less in cells concomitantly treated with IFN-γ. Furthermore, neutralisation of residual TNF-α activity or inhibition of NF-κB activation largely restored the inhibitory effect of IL-4. The data show that inhibition of IFN-γ-induced NO production by IL-4 is impaired by HSV-2 infection due to autocrine TNF-α-mediated NF-κB activation. We suggest that the described phenomenon might be beneficial for the host by limiting high and sustained NO production to infectious foci. 2000 Springer-Verlag/, Wien Paludan S. R. Department of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark, DK aut Ellermann-Eriksen S. Department of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark, DK aut Malmgaard L. Department of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark, DK aut Mogensen S. C. Department of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark, DK aut https://doi.org/10.1007/s007050050048 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s007050050048 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Paludan S. R. Department of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark, DK aut NATIONALLICENCE 700 1- Ellermann-Eriksen S. Department of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark, DK aut NATIONALLICENCE 700 1- Malmgaard L. Department of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark, DK aut NATIONALLICENCE 700 1- Mogensen S. C. Department of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark, DK aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer