Evidence map›Paper›PMID 38777155›Full record

ArticleThe Journal of allergy and clinical immunology2024

IL-4-STAT6 axis amplifies histamine-induced vascular endothelial dysfunction and hypovolemic shock.

James Krempski, Amnah Yamani, Lakshmi Narasimha Rao Thota, Sahiti Marella, Varsha Ganesan, Ankit Sharma, Atsunori Kaneshige, Longchuan Bai, Haibin Zhou, Paul S Foster and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of allergy and clinical immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
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

7 citing papers in PubMed.

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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

13 authors.

James KrempskiMary H. Weiser Food Allergy Center, Michigan Medicine, University of Michigan, Ann Arbor, Mich.
Amnah YamaniMary H. Weiser Food Allergy Center, Michigan Medicine, University of Michigan, Ann Arbor, Mich; Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
Lakshmi Narasimha Rao ThotaMary H. Weiser Food Allergy Center, Michigan Medicine, University of Michigan, Ann Arbor, Mich.
Sahiti MarellaDepartment of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, Mich.
Varsha GanesanMary H. Weiser Food Allergy Center, Michigan Medicine, University of Michigan, Ann Arbor, Mich; Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, Mich.
Ankit SharmaMary H. Weiser Food Allergy Center, Michigan Medicine, University of Michigan, Ann Arbor, Mich.
Atsunori KaneshigeDepartment of Internal Medicine, University of Michigan, Ann Arbor, Mich; Department of Pharmacology, University of Michigan, Ann Arbor, Mich; Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Mich.
Longchuan BaiDepartment of Internal Medicine, University of Michigan, Ann Arbor, Mich; Department of Pharmacology, University of Michigan, Ann Arbor, Mich; Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Mich.
Haibin ZhouDepartment of Internal Medicine, University of Michigan, Ann Arbor, Mich; Department of Pharmacology, University of Michigan, Ann Arbor, Mich; Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Mich.
Paul S FosterSchool of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, and Immune Health Program, Hunter Medical Research Institute, Newcastle, Australia.
Shaomeng WangDepartment of Internal Medicine, University of Michigan, Ann Arbor, Mich; Department of Pharmacology, University of Michigan, Ann Arbor, Mich; Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Mich.
Andrea T ObiConrad Jobst Vascular Research Laboratories, University of Michigan Medical School, Ann Arbor, Mich.
Simon P HoganMary H. Weiser Food Allergy Center, Michigan Medicine, University of Michigan, Ann Arbor, Mich; Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, Mich. Electronic address: sihogan@med.umich.edu.

Funding

Food Allergy and Goblet Cell Antigen PassagesR01AI112626 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HOGAN, SIMON PATRICK, NEWBERRY, RODNEY D · 2015 to 2019
$2.4M
Pro-Type 2 Goblet Cell Antigen Passages in Food Sensitization and ReactivityR37AI112626 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SIMON Patrick HOGAN, Rodney D Newberry · 2023 to 2026
$2.2M
IL-9-producing MC precursor ancestry and function in Food AllergyR56AI175165 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HOGAN, SIMON PATRICK · 2023 to 2023
$330k
NIAID NIH HHS R01 AI112626NIAID NIH HHS R37 AI112626NIAID NIH HHS R56 AI175165
6 · The paper itself

Abstract

backgroundMast cell-derived mediators induce vasodilatation and fluid extravasation, leading to cardiovascular failure in severe anaphylaxis. We previously revealed a synergistic interaction between the cytokine IL-4 and the mast cell-derived mediator histamine in modulating vascular endothelial (VE) dysfunction and severe anaphylaxis. The mechanism by which IL-4 exacerbates histamine-induced VE dysfunction and severe anaphylaxis is unknown.

objectiveWe sought to identify the IL-4-induced molecular processes regulating the amplification of histamine-induced VE barrier dysfunction and the severity of IgE-mediated anaphylactic reactions.

methodsRNA sequencing, Western blot, Ca

resultsIL-4 enhancement of histamine-induced VE barrier dysfunction was associated with increased VE-cadherin degradation, intracellular calcium flux, and phosphorylated Src levels and required transcription and de novo protein synthesis. RNA sequencing analyses of IL-4-stimulated VE cells identified dysregulation of genes involved in cell proliferation, cell development, and cell growth, and transcription factor motif analyses revealed a significant enrichment of differential expressed genes with putative STAT3 and STAT6 motif. IL-4 stimulation in EA.hy926 cells induced both serine residue 727 and tyrosine residue 705 phosphorylation of STAT3. Genetic and pharmacologic ablation of VE STAT3 activity revealed a role for STAT3 in basal VE barrier function; however, IL-4 enhancement and histamine-induced VE barrier dysfunction was predominantly STAT3 independent. In contrast, IL-4 enhancement and histamine-induced VE barrier dysfunction was STAT6 dependent. Consistent with this finding, pharmacologic knockdown of STAT6 abrogated IL-4-mediated amplification of histamine-induced hypovolemia.

conclusionsThese studies unveil a novel role of the IL-4/STAT6 signaling axis in the priming of VE cells predisposing to exacerbation of histamine-induced anaphylaxis.

Indexed as

AnaphylaxisHistamineInterleukin-4ShockSTAT6 Transcription FactorAnimalsCadherinsCell LineEndothelial CellsEndothelium, VascularHumansMaleMiceSignal TransductionSTAT3 Transcription FactorCadherinsHistamineInterleukin-4STAT3 Transcription FactorSTAT6 protein, humanSTAT6 Transcription FactorAnaphylaxishistamineIL-4transcriptionvascular endothelium

Identifiers

PMID38777155
PMCPMC13011994

What OpenQuestion holds

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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.