Mechanism of interferon-gamma mediated down-regulation of interleukin-10 gene expression

Molecular Immunology
Annette SchaeferLoems Ziegler-Heitbrock

Abstract

Expression of the anti-inflammatory cytokine IL-10 is suppressed by the pro-inflammatory interferon gamma but the mechanism of this action is unknown. We analysed activity of IL-10 promoter luciferase reporter constructs in transfected RPMI 8226.1 B cells that were treated at -2 h with IFNgamma (1000 U/ml) followed by stimulation with LPS (100 ng/ml) at 0 h. IFNgamma treatment suppressed LPS-induced IL-10 promoter activity in a construct carrying the -1044 promoter and also one containing the -195 promoter. The suppression was independent of the IRF-motif at -182 but involved the Stat-motif at -120. In gelshift analysis this Stat motif did bind LPS-induced Stat3 and with IFNgamma treatment it did, in addition, bind Stat1. ChIP analysis for detection of transcription factor binding to chromatin in intact cells demonstrated Stat3 binding to the proximal IL-10 promoter when cells are stimulated with LPS only. Treatment with IFNgamma only led to Stat1 binding in ChIP analysis and treatment with IFNgamma plus LPS led to reduced Stat3 binding while Stat1 binding remained high. Finally, LPS-induced activity of the trimeric Stat-motif in front of the luciferase reporter was suppressed by IFNgamma. These data demonstrate that IFNgamma d...Continue Reading

References

Jun 1, 1992·Current Opinion in Immunology·R de Waal MalefytJ E de Vries
Jan 1, 1991·Research in Immunology·J E de VriesH Spits
Dec 1, 1989·The Journal of Experimental Medicine·D F FiorentinoT R Mosmann
Aug 1, 1994·European Journal of Immunology·H W Ziegler-HeitbrockM Ströbel
Feb 1, 1993·The Journal of Experimental Medicine·P ChomaratP Miossec
Dec 1, 1996·American Journal of Respiratory Cell and Molecular Biology·J M van HaarstH A Drexhage
Jan 1, 1997·Annual Review of Immunology·U BoehmJ C Howard
Aug 5, 1999·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·R P DonnellyD S Finbloom
Sep 30, 2000·Immunology·H D Brightbill, R L Modlin
Aug 17, 2001·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·M L De BoerA S Cross
Dec 26, 2001·The Journal of Biological Chemistry·Masahide ToneHerman Waldmann
Dec 14, 2002·Immunity·Bernd ElserMin Li-Weber
Apr 17, 2003·Journal of the National Cancer Institute·Jean-Philippe HerbeuvalChristian Genin
Sep 23, 2003·Immunity·Fengdong ChengEduardo M Sotomayor
Oct 4, 2003·Journal of Leukocyte Biology·Kate SchroderDavid A Hume
Mar 17, 2004·Nature Immunology·Diego MaritanoValeria Poli
Jul 31, 2004·The Journal of Biological Chemistry·Yulan Qing, George R Stark
Feb 17, 2006·European Journal of Immunology·Jeffrey B VanDeusenMichael A Caligiuri
Jun 13, 2006·Proceedings of the National Academy of Sciences of the United States of America·Monika KasprzyckaMariusz A Wasik
Oct 27, 2011·The Journal of Biological Chemistry·Sebastian BiglioneAnne E Goldfeld

❮ Previous
Next ❯

Citations

Jan 21, 2010·Immunologic Research·Christian M Hedrich, Jay H Bream
Apr 20, 2014·Cancers·Richard L Carpenter, Hui-Wen Lo
Nov 1, 2018·Oncoimmunology·Neal BhutianiNejat K Egilmez
Dec 12, 2018·Frontiers in Genetics·Kay BoultonAndroniki Psifidi
Apr 23, 2017·Scientific Reports·Theresa NeuperJutta Horejs-Hoeck
Apr 13, 2020·European Journal of Pharmacology·Tohid GharibiBehzad Baradaran

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cajal Bodies & Gems

Cajal bodies or coiled bodies are dense foci of coilin protein. Gemini of Cajal bodies, or gems, are microscopically similar to Cajal bodies. It is believed that Cajal bodies play important roles in RNA processing while gems assist the Cajal bodies. Find the latest research on Cajal bodies and gems here.

B cells: Gene Expression

B lymphocytes are white blood cells that play a role in the adaptive immune system by secreting antibodies. Here is the latest research on gene expression in B cells.