Molecular mechanisms of IL-18BP regulation in DLD-1 cells: pivotal direct action of the STAT1/GAS axis on the promoter level
- Interleukin (IL)-18, formerly known as interferon (IFN)-γ-inducing factor, is a crucial mediator of host defence and inflammation. Control of IL-18 bioactivity by its endogenous antagonist IL-18 binding protein (IL-18BP) is a major objective of immunoregulation. IL-18BP is strongly up-regulated by IFN-γ, thereby establishing a negative feedback mechanism detectable in cell culture and in vivo. Here we sought to investigate in D.L. Dexter (DLD) colon carcinoma cells molecular mechanisms of IL-18BP induction under the influence of IFN-γ. Mutational analysis revealed that a proximal γ-activated sequence (GAS) at the IL-18BP promoter is of pivotal importance for expression by IFN-γ-activated cells. Use of siRNA underscored the essential role of the signal transducer and activator of transcription (STAT)-1 in this process. Indeed, electrophoretic mobility shift assay and chromatin immunoprecipitation analysis proved STAT1 binding to this particular GAS site. Maximal expression of IL-18BP was dependent on de novo protein synthesis but unaffected by silencing of interferon regulatory factor-1. Altogether, data presented herein indicate that direct action of STAT1 on the IL-18BP promoter at the proximal GAS element is key to IL-18BP expression by IFN-γ-stimulated DLD-1 colon carcinoma cells.
Author: | Malte BachmannGND, Jens Paulukat, Josef PfeilschifterGND, Heiko MühlORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-272751 |
DOI: | https://doi.org/10.1111/j.1582-4934.2008.00604.x |
ISSN: | 1582-4934 |
ISSN: | 1582-1838 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/19046253 |
Parent Title (English): | Journal of cellular and molecular medicine |
Publisher: | Wiley-Blackwell |
Place of publication: | Hoboken, NJ |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2008/11/28 |
Date of first Publication: | 2008/11/28 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2013/02/08 |
Tag: | IL-18 binding protein; STAT1; interferon-γ |
Volume: | 13 |
Issue: | 8b |
Page Number: | 8 |
First Page: | 1987 |
Last Page: | 1994 |
Note: | © 2008 The Authors Journal compilation © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. This is an Open Access article under the terms of the Creative Commons Attribution Non Commercial License http://creativecommons.org/licenses/by-nc/3.0/ which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
HeBIS-PPN: | 327687886 |
Institutes: | Medizin / Medizin |
Fachübergreifende Einrichtungen / Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit (ZAFES) | |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - Namensnennung-Nicht kommerziell 3.0 |