Evidence map›Paper›PMID 25098295›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2014

The Fli-1 transcription factor regulates the expression of CCL5/RANTES.

Mara L Lennard Richard, Shuzo Sato, Eiji Suzuki, Sarah Williams, Tamara K Nowling, Xian K Zhang

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

24 citing papers in PubMed, 41 citations in OpenAlex.

  1. IL-15 and IL-21 synergy improves anti-tumor efficacy of iPSC-derived cytotoxic T cells in solid tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
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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

6 authors at 2 institutions in 1 country.

Mara L Lennard RichardDivision of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425; and.
Shuzo SatoDivision of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425; and.
Eiji SuzukiDivision of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425; and.
Sarah WilliamsMedical Research Service, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC 29403.
Tamara K NowlingDivision of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425; and Medical Research Service, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC 29403.
Xian K ZhangDivision of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425; and Medical Research Service, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC 29403 zhangjo@musc.edu.
Medical University of South Carolina · USRalph H. Johnson VA Medical Center · US

Funding

SOUTH CAROLINA CLINICAL & TRANSLATIONAL RESEARCH INSTITUTE (SCTR)UL1RR029882 · NCRR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI BRADY, KATHLEEN T. · 2009 to 2011
$10.1M
South Carolina Clinical & Translational Research Institute (SCTR)UL1TR000062 · NCATS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI BRADY, KATHLEEN T. · 2012 to 2014
$9.4M
Molecular mechanisms of the impact of Fli-1 on lupusR01AR056670 · NIAMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI ZHANG, XIAN · 2010 to 2014
$1.4M
NCATS NIH HHS UL1 TR000062NCRR NIH HHS UL1 RR029882NIAMS NIH HHS AR056670NIAMS NIH HHS R01 AR056670
6 · The paper itself

Abstract

The friend leukemia insertion site 1 (Fli-1) transcription factor, an Ets family member, is implicated in the pathogenesis of systemic lupus erythematosus in human patients and murine models of lupus. Lupus-prone mice with reduced Fli-1 expression have significantly less nephritis, prolonged survival, and decreased infiltrating inflammatory cells into the kidney. Inflammatory chemokines, including CCL5, are critical for attracting inflammatory cells. In this study, decreased CCL5 mRNA expression was observed in kidneys of lupus-prone NZM2410 mice with reduced Fli-1 expression. CCL5 protein expression was significantly decreased in endothelial cells transfected with Fli-1-specific small interfering RNA compared with controls. Fli-1 binds to endogenous Ets binding sites in the distal region of the CCL5 promoter. Transient transfection assays demonstrate that Fli-1 drives transcription from the CCL5 promoter in a dose-dependent manner. Both Ets1, another Ets family member, and Fli-1 drive transcription from the CCL5 promoter, although Fli-1 transactivation was significantly stronger. Ets1 acts as a dominant-negative transcription factor for Fli-1, indicating that they may have at least one DNA binding site in common. Systematic deletion of DNA binding sites demonstrates the importance of the sites located within a 225-bp region of the promoter. Mutation of the Fli-1 DNA binding domain significantly reduces transactivation of the CCL5 promoter by Fli-1. We identified a novel regulator of transcription for CCL5. These results suggest that Fli-1 is a novel and critical regulator of proinflammatory chemokines and affects the pathogenesis of disease through the regulation of factors that recruit inflammatory cells to sites of inflammation.

Indexed as

3T3 CellsAnimalsBinding SitesCell LineChemokine CCL5DNADNA-Binding ProteinsEndothelial CellsInflammationKidneyLupus Erythematosus, SystemicMiceMice, TransgenicNephritisPromoter Regions, GeneticProto-Oncogene Protein c-ets-1Ccl5 protein, mouseChemokine CCL5DNADNA-Binding ProteinsEts1 protein, mouseFli1 protein, mouseProto-Oncogene Protein c-ets-1Proto-Oncogene Protein c-fli-1RNA, MessengerRNA, Small Interfering

Identifiers

PMID25098295
PMCPMC4157095
OpenAlexW1889803280

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.