Evidence map›Paper›PMID 25108845›Full record

ArticleMolecular immunology2015

Fli-1 controls transcription from the MCP-1 gene promoter, which may provide a novel mechanism for chemokine and cytokine activation.

Mara L Lennard Richard, Tamara K Nowling, Danielle Brandon, Dennis K Watson, Xian K Zhang

Open access · greenAbstract read
In one paragraph

Article in Molecular immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.0field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
  2. Review
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  4. Pericytes mediate neuroinflammation via Fli-1 in endotoxemia and sepsis in mice.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
    Article
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  18. Protective Effect of the Total Triterpenes ofEvidence-based complementary and alternative medicine : eCAM · 2019
    Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Mara L Lennard RichardDepartment of Medicine, Division of Rheumatology & Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
Tamara K NowlingDepartment of Medicine, Division of Rheumatology & Immunology, Medical University of South Carolina, Charleston, SC 29425, USA; Medical Research Service, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC 29403, USA.
Danielle BrandonDepartment of Medicine, Division of Rheumatology & Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
Dennis K WatsonDepartment of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA.
Xian K ZhangDepartment of Medicine, Division of Rheumatology & Immunology, Medical University of South Carolina, Charleston, SC 29425, USA; Medical Research Service, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC 29403, USA. Electronic address: zhangjo@musc.edu.
Medical University of South Carolina · USRalph H. Johnson VA Medical Center · US

Funding

Molecular mechanisms of the impact of Fli-1 on lupusR01AR056670 · NIAMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI ZHANG, XIAN · 2010 to 2014
$1.4M
NIAMS NIH HHS AR056670NIAMS NIH HHS R01 AR056670
6 · The paper itself

Abstract

Regulation of proinflammatory cytokines and chemokines is a primary role of the innate immune response. MCP-1 is a chemokine that recruits immune cells to sites of inflammation. Expression of MCP-1 is reduced in primary kidney endothelial cells from mice with a heterozygous knockout of the Fli-1 transcription factor. Fli-1 is a member of the Ets family of transcription factors, which are evolutionarily conserved across several organisms including Drosophilla, Xenopus, mouse and human. Ets family members bind DNA through a consensus sequence GGAA/T, or Ets binding site (EBS). Fli-1 binds to EBSs within the endogenous MCP-1 promoter by ChIP assay. In this study, transient transfection assays indicate that the Fli-1 gene actively promotes transcription from the MCP-1 gene promoter in a dose-dependent manner. Mutation of the DNA binding domain of Fli-1 demonstrated that Fli-1 activates transcription of MCP-1 both directly, by binding to the promoter, and indirectly, likely through interactions with other transcription factors. Another Ets transcription factor, Ets-1, was also tested, but failed to promote transcription. While Ets-1 failed to drive transcription independently, a weak synergistic activation of the MCP-1 promoter was observed between Ets-1 and Fli-1. In addition, Fli-1 and the NFκB family member p65 were found to interact synergistically to activate transcription from the MCP-1 promoter, while Sp1 and p50 inhibit this interaction. Deletion studies identified that EBSs in the distal and proximal MCP-1 promoter are critical for Fli-1 activation from the MCP-1 promoter. Together, these results demonstrate that Fli-1 is a novel regulator of the proinflammatory chemokine MCP-1, that interacts with other transcription factors to form a complex transcriptional mechanism for the activation of MCP-1 and mediation of the inflammatory response.

Indexed as

Promoter Regions, GeneticAnimalsBinding SitesChemokine CCL2HumansMiceMutationNIH 3T3 CellsProtein BindingProto-Oncogene Protein c-fli-1Sp1 Transcription FactorTranscriptional ActivationTranscription Factor RelATranscription, GeneticChemokine CCL2Proto-Oncogene Protein c-fli-1Sp1 Transcription FactorTranscription Factor RelAChemokinesFli-1Gene regulationInflammationMCP-1Transcriptional factors

Identifiers

PMID25108845
PMCPMC4254164
OpenAlexW1996580604

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.