Evidence map›Paper›PMID 27417329›Full record

ArticleBritish journal of pharmacology2016

Inhibition of spleen tyrosine kinase attenuates IgE-mediated airway contraction and mediator release in human precision cut lung slices.

Cynthia J Koziol-White, Yanlin Jia, Gretchen A Baltus, Philip R Cooper, Dennis M Zaller, Michael A Crackower, Erich E Sirkowski, Steven Smock, Alan B Northrup, Blanca E Himes and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in British journal of pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 17% 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

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.

  1. Pooled it
  2. Article
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  4. Article
  5. Review
  6. Review
  7. Article
  8. Human Lung Mast Cells: Therapeutic Implications in Asthma.International journal of molecular sciences · 2022
    Review
  9. Article
  10. Article
  11. Review
  12. Organotypic Models of Lung Cancer.Current topics in microbiology and immunology · 2021
    Article
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  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. 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

12 authors at 3 institutions in 1 country.

Cynthia J Koziol-WhiteRutgers Institute for Translational Medicine and Science, Child Health Institute, Rutgers University, New Brunswick, NJ, Canada.
Yanlin JiaMerck Research Laboratories, Boston, MA, USA.
Gretchen A BaltusMerck Research Laboratories, Boston, MA, USA.
Philip R CooperRutgers Institute for Translational Medicine and Science, Child Health Institute, Rutgers University, New Brunswick, NJ, Canada.
Dennis M ZallerMerck Research Laboratories, Boston, MA, USA.
Michael A CrackowerMerck Research Laboratories, Boston, MA, USA.
Erich E SirkowskiMerck Research Laboratories, Boston, MA, USA.
Steven SmockMerck Research Laboratories, Boston, MA, USA.
Alan B NorthrupMerck Research Laboratories, Boston, MA, USA.
Blanca E HimesDepartment of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA.
Stephen E AlvesMerck Research Laboratories, Boston, MA, USA.
Reynold A PanettieriRutgers Institute for Translational Medicine and Science, Child Health Institute, Rutgers University, New Brunswick, NJ, Canada. rp856@ca.rutgers.edu.
Merck & Co., Inc., Rahway, NJ, USA (United States) · USRutgers, The State University of New Jersey · USUniversity of Pennsylvania · US

Funding

Translational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI A. Clementina Mesaros · 2006 to 2026
$35.3M
INTEGRATIVE GENOMICS APPROACHES TO MODEL THE GENETIC ARCHITECTURE OF ASTHMAR00HL105663 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI HIMES, BLANCA E · 2013 to 2015
$702k
NHLBI NIH HHS R00 HL105663NIEHS NIH HHS P30 ES013508
6 · The paper itself

Abstract

background and purposeAsthma presents as a heterogeneous syndrome characterized by airway obstruction, inflammation and hyper-reactivity (AHR). Spleen tyrosine kinase (Syk) mediates allergen-induced mast cell degranulation, a central component of allergen-induced inflammation and AHR. However, the role of Syk in IgE-mediated constriction of human small airways remains unknown. In this study, we addressed whether selective inhibition of Syk attenuates IgE-mediated constriction and mast cell mediator release in human small airways. EXPERIMENTAL APPROACH: Human precision cut lung slices (hPCLS) ex vivo derived from non-asthmatic donors were incubated overnight with human IgE, dexamethasone, montelukast, antihistamines or a selective Syk inhibitor (SYKi). High-affinity IgE receptor (FcεRI) activation by anti-IgE cross-linking was performed, and constriction and mediator release measured. Airway constriction was normalized to that induced by maximal carbachol stimulation. Syk expression (determined by qPCR and immunoblot) was also evaluated in human primary airway smooth muscle (HASM) cells to determine whether Syk directly modulates HASM function. KEY

resultsWhile dexamethasone had little effect on FcεR-mediated contraction, montelukast or antihistamines partially attenuated the response. SYKi abolished anti-IgE-mediated contraction and suppressed the release of mast cell or basophil mediators from the IgE-treated hPCLS. In contrast, SYKi had little effect on the non-allergic contraction induced by carbachol. Syk mRNA and protein were undetectable in HASM cells. CONCLUSIONS AND IMPLICATIONS: A selective Syk inhibitor, but not corticosteroids, abolished FcεR-mediated contraction in human small airways ex vivo. The mechanism involved FcεRI receptor activation on mast cells or basophils that degranulate causing airway constriction, rather than direct actions on HASM.

Indexed as

Cells, CulturedHumansImmunoglobulin EIn Vitro TechniquesLungMuscle ContractionMuscle, SmoothProtein Kinase InhibitorsProtein-Tyrosine KinasesSpleenImmunoglobulin EProtein Kinase InhibitorsProtein-Tyrosine Kinases

Identifiers

PMID27417329
PMCPMC5056227
OpenAlexW2506452942

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.