Evidence map›Paper›PMID 27001469›Full record

ArticleImmunology and cell biology2016

Human eosinophil activin A synthesis and mRNA stabilization are induced by the combination of IL-3 plus TNF.

Elizabeth A Kelly, Stephane Esnault, Sean H Johnson, Lin Ying Liu, James S Malter, Mandy E Burnham, Nizar N Jarjour

Open access · bronzeAbstract read
In one paragraph

Article in Immunology and cell biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

12 citing papers in PubMed, 21 citations in OpenAlex.

  1. Identification of the Cytokines, Growth Factors and Their Receptors Expressed by Human Blood Eosinophils: A Transcriptomics Approach.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2025
    Article
  2. Article
  3. Article
  4. Tumor Necrosis Factor Alpha Signaling and Organogenesis.Frontiers in cell and developmental biology · 2021
    Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Mepolizumab Attenuates Airway Eosinophil Numbers, but Not Their Functional Phenotype, in Asthma.American journal of respiratory and critical care medicine · 2017
    Article
  10. IL-3 up-regulates and activates human eosinophil CD32 and αMβ2 integrin causing degranulation.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2017
    Article
  11. Review
  12. Review
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

7 authors at 2 institutions in 1 country.

Elizabeth A KellyAllergy, Pulmonary and Critical Care Medicine Division, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.ORCID 0000-0001-7335-6698
Stephane EsnaultAllergy, Pulmonary and Critical Care Medicine Division, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Sean H JohnsonAllergy, Pulmonary and Critical Care Medicine Division, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Lin Ying LiuAllergy, Pulmonary and Critical Care Medicine Division, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
James S MalterDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Mandy E BurnhamDepartment of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Nizar N JarjourAllergy, Pulmonary and Critical Care Medicine Division, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
University of Wisconsin–Madison · USThe University of Texas Southwestern Medical Center · US

Funding

Institutional Clinical and Translational Science AwardUL1TR000427 · NCATS · UNIVERSITY OF WISCONSIN-MADISON · PI DREZNER, MARC KENNETH · 2012 to 2016
$32.2M
INSTITUTIONAL CTSA (UW-MADISON): CLINICAL TRIALSUL1RR025011 · NCRR · UNIVERSITY OF WISCONSIN-MADISON · PI DREZNER, MARC KENNETH · 2007 to 2011
$29.5M
Thr Role of Pin1 in AirwayP01HL088594 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI JARJOUR, NIZAR N · 2008 to 2017
$21.0M
ZOSUQUIDAR TRIHYDROCHLORIDE IN NEWLY DIAGNOSED AMLM01RR003186 · NCRR · UNIVERSITY OF WISCONSIN-MADISON · PI TRAYNOR, ANNE M · 1986 to 2007
$19.3M
SCOR--CELLULAR AND MOLECULAR MECHANISMS OF ASTHMAP50HL056396 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI MALTER, JAMES S · 1997 to 2006
$13.8M
Pin1 regulation of prosurvival signalling in eosinophilsR01HL087950 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI MALTER, JAMES S · 2008 to 2011
$1.5M
NCATS NIH HHS UL1 TR000427NCRR NIH HHS M01 RR003186NCRR NIH HHS UL1 RR025011NHLBI NIH HHS P01 HL088594NHLBI NIH HHS P50 HL056396NHLBI NIH HHS R01 HL087950
6 · The paper itself

Abstract

Eosinophils contribute to immune regulation and wound healing/fibrosis in various diseases, including asthma. Growing appreciation for the role of activin A in such processes led us to hypothesize that eosinophils are a source of this transforming growth factor-ß superfamily member. Tumor necrosis factor-α (TNF) induces activin A by other cell types and is often present at the site of allergic inflammation along with the eosinophil-activating common ß (ßc) chain-signaling cytokines (interleukin (IL)-5, IL-3, granulocyte-macrophages colony-stimulating factor (GM-CSF)). Previously, we established that the combination of TNF plus a ßc chain-signaling cytokine synergistically induces eosinophil synthesis of the remodeling enzyme matrix metalloproteinase-9. Therefore, eosinophils were stimulated ex vivo by these cytokines and in vivo through an allergen-induced airway inflammatory response. In contrast to IL-5+TNF or GM-CSF+TNF, the combination of IL-3+TNF synergistically induced activin A synthesis and release by human blood eosinophils. IL-3+TNF enhanced activin A mRNA stability, which required sustained signaling of pathways downstream of p38 and extracellular signal-regulated kinase mitogen-activated protein kinases. In vivo, following segmental airway allergen challenge of subjects with mild allergic asthma, activin A mRNA was upregulated in airway eosinophils compared with circulating eosinophils, and ex vivo, circulating eosinophils tended to release more activin A in response to IL-3+TNF. These data provide evidence that eosinophils release activin A and that this function is enhanced when eosinophils are present in an allergen-induced inflammatory environment. Moreover, these data provide the first evidence for posttranscriptional control of activin A mRNA. We propose that an environment rich in IL-3+TNF will lead to eosinophil-derived activin A, which has an important role in regulating inflammation and/or fibrosis.

Indexed as

RNA StabilityActivinsAdultEnzyme ActivationEosinophilsFemaleGranulocyte-Macrophage Colony-Stimulating FactorHumansHypersensitivityInhibin-beta SubunitsInterleukin-3Interleukin-5KineticsMaleMiddle AgedMitogen-Activated Protein Kinasesactivin AActivinsGranulocyte-Macrophage Colony-Stimulating Factorinhibin beta A subunitInhibin-beta SubunitsInterleukin-3Interleukin-5Mitogen-Activated Protein KinasesNF-kappa BProtein Kinase InhibitorsRNA, MessengerTumor Necrosis Factor-alpha

Identifiers

PMID27001469
PMCPMC4980187
OpenAlexW2306103113

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.