| Title |
The signal transducers Stat1 and Stat3 and their novel target Jmjd3 drive the expression of inflammatory genes in microglia
|
|---|---|
| Published in |
Journal of Molecular Medicine, October 2013
|
| DOI | 10.1007/s00109-013-1090-5 |
| Pubmed ID | |
| Authors |
Piotr Przanowski, Michal Dabrowski, Aleksandra Ellert-Miklaszewska, Michal Kloss, Jakub Mieczkowski, Beata Kaza, Anna Ronowicz, Feng Hu, Arkadiusz Piotrowski, Helmut Kettenmann, Jan Komorowski, Bozena Kaminska |
| Abstract |
Most neurological diseases are associated with chronic inflammation initiated by the activation of microglia, which produce cytotoxic and inflammatory factors. Signal transducers and activators of transcription (STATs) are potent regulators of gene expression but contribution of particular STAT to inflammatory gene expression and STAT-dependent transcriptional networks underlying brain inflammation need to be identified. In the present study, we investigated the genomic distribution of Stat binding sites and the role of Stats in the gene expression in lipopolysaccharide (LPS)-activated primary microglial cultures. Integration of chromatin immunoprecipitation-promoter microarray data and transcriptome data revealed novel Stat-target genes including Jmjd3, Ccl5, Ezr, Ifih1, Irf7, Uba7, and Pim1. While knockdown of individual Stat had little effect on the expression of tested genes, knockdown of both Stat1 and Stat3 inhibited the expression of Jmjd3 and inflammatory genes. Transcriptional regulation of Jmjd3 by Stat1 and Stat3 is a novel mechanism crucial for launching inflammatory responses in microglia. The effects of Jmjd3 on inflammatory gene expression were independent of its H3K27me3 demethylase activity. Forced expression of constitutively activated Stat1 and Stat3 induced the expression of Jmjd3, inflammation-related genes, and the production of pro-inflammatory cytokines as potently as lipopolysacharide. Gene set enrichment and gene function analysis revealed categories linked to the inflammatory response in LPS and Stat1C + Stat3C groups. We defined upstream pathways that activate STATs in response to LPS and demonstrated contribution of Tlr4 and Il-6 and interferon-γ signaling. Our findings define novel direct transcriptional targets of Stat1 and Stat3 and highlight their contribution to inflammatory gene expression. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Hungary | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 129 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Netherlands | 1 | <1% |
| Ukraine | 1 | <1% |
| Unknown | 127 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 32 | 25% |
| Researcher | 23 | 18% |
| Student > Bachelor | 15 | 12% |
| Student > Master | 11 | 9% |
| Student > Doctoral Student | 9 | 7% |
| Other | 19 | 15% |
| Unknown | 20 | 16% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 27 | 21% |
| Agricultural and Biological Sciences | 27 | 21% |
| Neuroscience | 19 | 15% |
| Medicine and Dentistry | 13 | 10% |
| Immunology and Microbiology | 5 | 4% |
| Other | 14 | 11% |
| Unknown | 24 | 19% |
Attention Score in Context
This research output has an Altmetric Attention Score of 27. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 April 2020.
All research outputs
#1,213,862
of 22,725,280 outputs
Outputs from Journal of Molecular Medicine
#28
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Outputs of similar age
#12,045
of 208,527 outputs
Outputs of similar age from Journal of Molecular Medicine
#1
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