IFN-gamma and IL-4 differently regulate inducible NO synthase gene expression through IRF-1 modulation.

International immunology (2000-07-06)
E M Coccia, E Stellacci, G Marziali, G Weiss, A Battistini

NO is a labile radical involved in several immunological, antimicrobial and inflammatory processes. In macrophages, NO formation is catalyzed by the cytokine-inducible enzyme inducible NO synthase (iNOS). The importance of IFN regulatory factor (IRF)-1 and of the signal transducers and activators of transcription (STAT)-1 for the induction of iNOS gene expression in response to IFN-gamma has been well defined. Here, we investigated the molecular events responsible for the inhibition of iNOS gene expression by IL-4 in the murine macrophage cell line RAW264.7. Unidirectional deletion analysis on iNOS promoter demonstrated that an IFN-stimulated responsive element (ISRE), contained in the -980 to -765 bp region of the iNOS promoter, may be involved in the IL-4-mediated inhibition of IFN-gamma-inducible iNOS transcription. Accordingly, the IFN-gamma-induced binding activity of IRF-1 to the ISRE sequence was reduced in cells pre-treated with IL-4, while the binding activity of STAT-1 to the STAT-binding element (SBE) within the same region of the iNOS promoter remained unaffected. Moreover, IL-4 even down-regulated IFN-gamma-inducible expression of IRF-1 mRNA. This could be related to a transcriptional mechanism by which IL-4 and IFN-gamma differentially influence the trans-acting activity of the STAT factors binding to SBE within the IRF-1 promoter. SBE is targeted by IFN-gamma-inducible STAT-1 and by IL-4-inducible STAT-6. Although STAT-6 has no trans-acting function on iNOS gene expression, it is able to inhibit the IFN-gamma-induced expression of IRF-1. Thus, IL-4 may down-regulate IFN-gamma-inducible iNOS transcription by activation of STAT-6 which in turn inhibits IRF-1 expression.

Referencia del producto
Descripción del producto

Monoclonal Anti-Interleukin-4 antibody produced in mouse, clone 3007, purified immunoglobulin, lyophilized powder
Monoclonal Anti-Interleukin-4 antibody produced in mouse, clone 3010, purified immunoglobulin, lyophilized powder
Anti-Interleukin-4 Soluble Receptor antibody produced in goat, IgG fraction of antiserum, lyophilized powder
Anti-Interleukin-4 antibody produced in goat, affinity isolated antibody, lyophilized powder

Redes sociales

LinkedIn icon
Twitter icon
Facebook Icon
Instagram Icon


Investigación. Desarrollo. Producción.

Somos un proveedor líder para la industria de Ciencias de la Vida con soluciones y servicios para investigación, desarrollo y producción biotecnológicos, y para desarrollo y producción de tratamientos farmacéuticos

© 2021 Merck KGaA, Darmstadt, Alemania y/o sus filiales. Todos los derechos reservados.

Queda estrictamente prohibida la reproducción sin permiso de cualquiera de los materiales de la página web.