NDLI: Early inhibition of IL-1ß expression by IFN-Î³ is mediated by impaired binding of NF-κB to the IL-1ß promoter but is independent of nitric oxide.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Eigenbrod, Tatjana Bode, Konrad A. Dalpke, Alexander H.
Description	Country affiliation: Germany Author Affiliation: Eigenbrod T ( Department of Infectious Diseases, Medical Microbiology, and Hygiene, University of Heidelberg, 69120 Heidelberg, Germany. tatjana.eigenbrod@med.uni-heidelberg.de)
Abstract	The significance of bacterial RNA recognition for initiating innate immune responses against invading pathogens has only recently started to be elucidated. Bacterial RNA is an important trigger of inflammasome activation, resulting in caspase-1-dependent cleavage of pro-IL-1ß into the active form. It was reported previously that prolonged treatment with IFN-Î³ can inhibit IL-1ß production at the level of both transcription and Nlrp3 inflammasome activation in an NO-dependent manner. As a result of the delayed kinetics of NO generation after IFN-Î³ stimulation, these effects were only observed at later time points. We report that IFN-Î³ suppressed bacterial RNA and LPS induced IL-1ß transcription in primary murine macrophages and dendritic cells by an additional, very rapid mechanism that was independent of NO. Costimulation with IFN-Î³ selectively attenuated binding of NF-κB p65 to the IL-1ß promoter, thus representing a novel mechanism of IL-1ß inhibition by IFN-Î³. Transcriptional silencing was specific for IL-1ß because expression of other proinflammatory cytokines, such as TNF, IL-6, and IL-12p40, was not affected. Furthermore, by suppressing IL-1ß production, IFN-Î³ impaired differentiation of Th17 cells and production of neutrophil chemotactic factor CXCL1 in vitro. The findings provide evidence for a rapid immune-modulating effect of IFN-Î³ independent of NO.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	12
Volume Number	190
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2013-06-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Immunity, Innate Immunology Interferon-gamma Metabolism Interleukin-1beta Biosynthesis Nf-kappa B Promoter Regions, Genetic Animals Blotting, Western Cell Differentiation Chromatin Immunoprecipitation Genetics Lymphocyte Activation Mice Mice, Inbred C57bl Mice, Knockout Nitric Oxide Rna, Bacterial Real-time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Th17 Cells Cytology Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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