Evidence map›Paper›PMID 25918170›Full record

ArticleThe Journal of biological chemistry2015

Transforming Growth Factor-β and Interleukin-1β Signaling Pathways Converge on the Chemokine CCL20 Promoter.

Oliver J Brand, Sangeeta Somanath, Catherine Moermans, Haruhiko Yanagisawa, Mitsuo Hashimoto, Stephanie Cambier, Jennifer Markovics, Andrew J Bondesson, Arthur Hill, David Jablons and 5 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

25 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
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  5. Review
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  9. Review
  10. P2YPurinergic signalling · 2023
    Review
  11. Article
  12. The P2YCellular and molecular life sciences : CMLS · 2022
    Article
  13. Review
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  15. Article
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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

15 authors at 2 institutions in 1 country.

Oliver J BrandFrom the Departments of Pathology.
Sangeeta SomanathFrom the Departments of Pathology.
Catherine MoermansFrom the Departments of Pathology.
Haruhiko YanagisawaFrom the Departments of Pathology.
Mitsuo HashimotoFrom the Departments of Pathology.
Stephanie CambierFrom the Departments of Pathology.
Jennifer MarkovicsFrom the Departments of Pathology.
Andrew J BondessonFrom the Departments of Pathology.
Arthur HillSurgery, University of California, San Francisco, California 94110.
David JablonsSurgery, University of California, San Francisco, California 94110.
Paul WoltersMedicine, and.
Jianlong LouAnesthesia and Perioperative Care.
James D MarksAnesthesia and Perioperative Care.
Jody L BaronMedicine, and.
Stephen L NishimuraFrom the Departments of Pathology, stephen.nishimura@ucsf.edu.
Association of Perioperative Registered Nurses · USUniversity of California, San Francisco · US

Funding

UCSF Liver Core CenterP30DK026743 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Holger Willenbring · 1986 to 2026
$30.7M
UC BRAID Center for Accelerated Innovation COVID-19 diagnostic project developmentU54HL119893 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PALAZZOLO, MICHAEL J · 2013 to 2020
$18.3M
Underlying mechanisms for the pro-angiogenic phenotype of AVMsP01NS044155 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SU, HUA · 2003 to 2013
$12.8M
Integrin avB8 Inhibits Airway Epithelial Cell GrowthR01HL063993 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI NISHIMURA, STEPHEN L · 2001 to 2011
$3.3M
Role of genetic variation in TGF-beta overactivation in COPDR01HL113032 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI NISHIMURA, STEPHEN L · 2012 to 2015
$2.1M
Role of Squamous Metaplasia in Small Airways Disease in COPDR01HL090662 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI NISHIMURA, STEPHEN L · 2009 to 2010
$953k
NHLBI NIH HHS HL063993NHLBI NIH HHS HL090662NHLBI NIH HHS HL113032NHLBI NIH HHS R01 HL063993NHLBI NIH HHS R01 HL090662NHLBI NIH HHS R01 HL113032NHLBI NIH HHS U54 HL119893NHLBI NIH HHS U54HL119893NIDDK NIH HHS P30 DK026743NIDDK NIH HHS P30DK026743NINDS NIH HHS NS044155NINDS NIH HHS P01 NS044155
6 · The paper itself

Abstract

CCL20 is the only chemokine ligand for the chemokine receptor CCR6, which is expressed by the critical antigen presenting cells, dendritic cells. Increased expression of CCL20 is likely involved in the increased recruitment of dendritic cells observed in fibroinflammatory diseases such as chronic obstructive pulmonary disease (COPD). CCL20 expression is increased by the proinflammatory cytokine IL-1β. We have determined that IL-1β-dependent CCL20 expression is also dependent on the multifunctional cytokine TGF-β. TGF-β is expressed in a latent form that must be activated to function, and activation is achieved through binding to the integrin αvβ8 (itgb8). Here we confirm correlative increases in αvβ8 and IL-1β with CCL20 protein in lung parenchymal lysates of a large cohort of COPD patients. How IL-1β- and αvβ8-mediated TGF-β activation conspire to increase fibroblast CCL20 expression remains unknown, because these pathways have not been shown to directly interact. We evaluate the 5'-flanking region of CCL20 to determine that IL-1β-driven CCL20 expression is dependent on αvβ8-mediated activation of TGF-β. We identify a TGF-β-responsive element (i.e. SMAD) located on an upstream enhancer of the human CCL20 promoter required for efficient IL-1β-dependent CCL20 expression. By chromatin immunoprecipitation, this upstream enhancer complexes with the p50 subunit of NF-κB on a NF-κB-binding element close to the transcriptional start site of CCL20. These interactions are confirmed by electromobility shift assays in nuclear extracts from human lung fibroblasts. These data define a mechanism by which αvβ8-dependent activation of TGF-β regulates IL-1β-dependent CCL20 expression in COPD.

Indexed as

Response ElementsSignal TransductionAnimalsBase SequenceCells, CulturedChemokine CCL20FibroblastsGene Expression RegulationHumansInterleukin-1betaLungMiceMice, Inbred C57BLNF-kappa BTransforming Growth Factor betaCCL20 protein, humanChemokine CCL20Interleukin-1betaNF-kappa BTransforming Growth Factor betachemokineinflammationintegrinTGF-βtranscription

Identifiers

PMID25918170
PMCPMC4505537
OpenAlexW2091286425

What OpenQuestion holds

Textmetadata
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.