The Fli-1 transcription factor is a critical regulator for controlling the expression of chemokine C-X-C motif ligand 2 (CXCL2)
Copyright © 2016. Published by Elsevier Ltd..
Mammalian cells produce inflammatory cytokines and chemokines in response to innate immune signals and their expression is tightly regulated. Chemokine (C-X-C motif) ligand 2 (CXCL2), also known as macrophage inflammatory protein 2-alpha (MIP2-alpha), is an inflammatory chemokine belonging to the CXC chemokine family. CXCL2 is chemotactic for neutrophils and elevated expression of CXCL2 is associated with many inflammatory and autoimmune diseases. The Fli-1 gene belongs to the large Ets transcription factor family, whose members regulate a wide variety of cellular functions including the immune response. In this study, we demonstrate that endothelial cells transfected with Fli-1 specific siRNA produce significantly less CXCL2 compared to cells transfected with control siRNA after stimulation by the Toll-like receptor (TLR) 4 ligands, lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNF-α). The production of CXCL2 in endothelial cells stimulated with LPS stimulation is dose-dependent. We found that Fli-1 binds to the CXCL2 promoter as established by Chromatin immunoprecipitation (ChIP) assay. Transient transfection assays show that Fli-1 drives transcription from the CXCL2 promoter in a dose-dependent manner and Fli-1 regulates the expression of CXCL2 largely by directly binding to the promoter. Targeted knockdown and transient transfection experiments suggest that both Fli-1 and the p65 subunit of NF-κB affect the activation of CXCL2 in an additive manner. These results indicate that Fli-1 is a novel, critical transcription factor that regulates the expression of the inflammatory chemokine CXCL2.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:81 |
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| Enthalten in: |
Molecular immunology - 81(2017) vom: 02. Jan., Seite 59-66 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lou, Ning [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.09.2017 Date Revised 31.01.2018 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.molimm.2016.11.007 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM266575811 |
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| 245 | 1 | 4 | |a The Fli-1 transcription factor is a critical regulator for controlling the expression of chemokine C-X-C motif ligand 2 (CXCL2) |
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| 500 | |a Date Revised 31.01.2018 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2016. Published by Elsevier Ltd. | ||
| 520 | |a Mammalian cells produce inflammatory cytokines and chemokines in response to innate immune signals and their expression is tightly regulated. Chemokine (C-X-C motif) ligand 2 (CXCL2), also known as macrophage inflammatory protein 2-alpha (MIP2-alpha), is an inflammatory chemokine belonging to the CXC chemokine family. CXCL2 is chemotactic for neutrophils and elevated expression of CXCL2 is associated with many inflammatory and autoimmune diseases. The Fli-1 gene belongs to the large Ets transcription factor family, whose members regulate a wide variety of cellular functions including the immune response. In this study, we demonstrate that endothelial cells transfected with Fli-1 specific siRNA produce significantly less CXCL2 compared to cells transfected with control siRNA after stimulation by the Toll-like receptor (TLR) 4 ligands, lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNF-α). The production of CXCL2 in endothelial cells stimulated with LPS stimulation is dose-dependent. We found that Fli-1 binds to the CXCL2 promoter as established by Chromatin immunoprecipitation (ChIP) assay. Transient transfection assays show that Fli-1 drives transcription from the CXCL2 promoter in a dose-dependent manner and Fli-1 regulates the expression of CXCL2 largely by directly binding to the promoter. Targeted knockdown and transient transfection experiments suggest that both Fli-1 and the p65 subunit of NF-κB affect the activation of CXCL2 in an additive manner. These results indicate that Fli-1 is a novel, critical transcription factor that regulates the expression of the inflammatory chemokine CXCL2 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a CXCL2 | |
| 650 | 4 | |a Chemokine | |
| 650 | 4 | |a Inflammation | |
| 650 | 4 | |a Lipopolysaccharide (LPS) | |
| 650 | 4 | |a Toll-like receptor (TLR) | |
| 650 | 4 | |a Transcription factor Fli-1 | |
| 650 | 7 | |a Chemokine CXCL2 |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Protein c-fli-1 |2 NLM | |
| 700 | 1 | |a Lennard Richard, Mara L |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Jin |e verfasserin |4 aut | |
| 700 | 1 | |a Kindy, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xian K |e verfasserin |4 aut | |
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