Anti-Inflammatory Cytokine Interleukin-4 Inhibits Inducible Nitric Oxide Synthase Gene Expression in the Mouse Macrophage Cell Line RAW264.7 through the Repression of Octamer-Dependent Transcription
Joint Authors
Hiroi, Miki
Sakaeda, Yoshiichi
Ohmori, Yoshihiro
Yamaguchi, Hana
Source
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-12-29
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
Inducible nitric oxide synthase (iNOS) is a signature molecule involved in the classical activation of M1 macrophages and is induced by the Nos2 gene upon stimulation with Th1-cell derived interferon-gamma (IFNγ) and bacterial lipopolysaccharide (LPS).
Although the anti-inflammatory cytokine IL-4 is known to inhibit Nos2 gene expression, the molecular mechanism involved in the negative regulation of Nos2 by IL-4 remains to be fully elucidated.
In the present study, we investigated the mechanism of IL-4-mediated Nos2 transcriptional repression in the mouse macrophage-like cell line RAW264.7.
Signal transducer and activator of transcription 6 (Stat6) knockdown by siRNA abolished the IL-4-mediated inhibition of Nos2 induced by IFNγ/LPS.
Transient transfection of a luciferase reporter gene containing the 5′-flanking region of the Nos2 gene demonstrated that an octamer transcription factor (OCT) binding site in the promoter region is required for both positive regulation by IFNγ/LPS and negative regulation by IL-4.
Although IL-4 had no inhibitory effect on the DNA-binding activity of constitutively expressed Oct-1, IL-4-induced Nos2-reporter transcriptional repression was partially attenuated by overexpression of the coactivator CREB-binding protein (CBP).
These results suggest that a coactivator/cofactor that functionally interacts with Oct-1 is a molecular target for the IL-4-mediated inhibition of Nos2 and that IL-4-activated Stat6 represses Oct-1-dependent transcription by competing with this coactivator/cofactor.
American Psychological Association (APA)
Hiroi, Miki& Sakaeda, Yoshiichi& Yamaguchi, Hana& Ohmori, Yoshihiro. 2013. Anti-Inflammatory Cytokine Interleukin-4 Inhibits Inducible Nitric Oxide Synthase Gene Expression in the Mouse Macrophage Cell Line RAW264.7 through the Repression of Octamer-Dependent Transcription. Mediators of Inflammation،Vol. 2013, no. 2013, pp.1-14.
https://search.emarefa.net/detail/BIM-466595
Modern Language Association (MLA)
Hiroi, Miki…[et al.]. Anti-Inflammatory Cytokine Interleukin-4 Inhibits Inducible Nitric Oxide Synthase Gene Expression in the Mouse Macrophage Cell Line RAW264.7 through the Repression of Octamer-Dependent Transcription. Mediators of Inflammation No. 2013 (2013), pp.1-14.
https://search.emarefa.net/detail/BIM-466595
American Medical Association (AMA)
Hiroi, Miki& Sakaeda, Yoshiichi& Yamaguchi, Hana& Ohmori, Yoshihiro. Anti-Inflammatory Cytokine Interleukin-4 Inhibits Inducible Nitric Oxide Synthase Gene Expression in the Mouse Macrophage Cell Line RAW264.7 through the Repression of Octamer-Dependent Transcription. Mediators of Inflammation. 2013. Vol. 2013, no. 2013, pp.1-14.
https://search.emarefa.net/detail/BIM-466595
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-466595