Effect of IL-4 and IL-13 on IFN-gamma-induced production of nitric oxide in mouse macrophages infected with herpes simplex virus type 2.
Interleukin (IL)-4 and IL-13 share a wide range of activities. Prominent among these is the ability to antagonize many interferon (IFN)-gamma-induced activities. Here we demonstrate that IL-4 and IL-13 totally abrogate IFN-gamma-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) mRNA and protein synthesis in a murine macrophage cell line. IFN-gamma-treated cells infected with herpes simplex virus type 2 (HSV-2) or costimulated with tumor necrosis factor (TNF)-alpha showed an enhanced reactivity, which was only partially reduced by IL-4/13. The results indicate that IL-4 and IL-13 function by intervening with a step prior to iNOS transcription by antagonizing IFN-gamma-induced signal(s) without counteracting synergistic virus- or TNF-alpha-induced signals. The beneficial effect of a sustained NO production in foci of virus infection is suggested.
Paludan
S R
SR
Department of Medical Microbiology and Immunology, University of Aarhus, Aarhus C, Denmark. paludan@svfcd.aau.dk
Lovmand
J
J
Ellermann-Eriksen
S
S
Mogensen
S C
SC
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018258:Herpesvirus 2, Human / Q000502:physiology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism* / Q000821:virology; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004791:Enzyme Inhibitors; D018793:Interleukin-13; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D019311:Staurosporine