Evidence map›Paper›PMID 20053395›Full record

ArticleCellular immunology2010

Comparison of the anti-allergic activity of Syk inhibitors with optimized Syk siRNAs in FcepsilonRI-activated RBL-2H3 basophilic cells.

Michael P Sanderson, Stephen J Gelling, Jörg F Rippmann, Andreas Schnapp

Abstract readComparative Study
In one paragraph

Article in Cellular immunology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.0field-weighted citation impact, top 24% 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

6 citing papers in PubMed, 21 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Gene therapy for allergic airway diseases.Current allergy and asthma reports · 2011
    Review
  6. Fostamatinib Disodium.Drugs of the future · 2011
    Article
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

4 authors at 1 institution in 1 country.

Michael P SandersonDepartment of Pulmonary Diseases Research, Boehringer-Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany. michael.sanderson@boehringer-ingelheim.com
Stephen J Gelling
Jörg F Rippmann
Andreas Schnapp
Boehringer Ingelheim (Germany) · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Spleen tyrosine kinase (Syk) binds ITAM-bearing receptors in a wide variety of cell types. One such example is the activation of mast cells, basophils and eosinophils via the stimulation of the FcepsilonRI receptor by IgE/allergen complexes. The possible role of Syk in inflammatory signaling cascades has led to the development of pharmacological agents designed to block the Syk catalytic domain as potential novel therapeutics. Whilst the enzymatic activity of Syk lends towards the design of small-molecule inhibitors, other attention has focused on the possibility of targeting Syk expression using anti-sense oligonucleotides as an alternate means of anti-inflammatory therapy. In this study, we compared the ability of multiple optimized Syk siRNA sequences and small-molecule Syk inhibitors to block FcepsilonRI-mediated signal transduction, degranulation and TNFalpha secretion in the basophilic cell line RBL-2H3. We also characterized the specificity of each siRNA sequence with regards to off-target induction of the interferon-inducible gene IFIT1. We identified a single siRNA sequence, which displayed a favorable profile of efficient Syk knockdown, blockage of FcepsilonRI-mediated signal transduction, degranulation and TNFalpha secretion and a lack of IFIT1 induction. The effect of this siRNA was comparable to that of the Syk kinase domain inhibitors BAY61-3606 and R406. The identification of an active and specific Syk siRNA could be a basis for the development of therapeutic Syk siRNAs against inflammatory diseases.

Indexed as

AnimalsAnti-Allergic AgentsBasophilsCell LineGene Expression Regulation, EnzymologicHumansIntracellular Signaling Peptides and ProteinsMiceNiacinamideOxazinesProtein Kinase InhibitorsProtein-Tyrosine KinasesPyridinesPyrimidinesRatsReceptors, IgE2-(7-(3,4-dimethoxyphenyl)imidazo(1,2-c)pyrimidin-5-ylamino)nicotinamideAnti-Allergic AgentsIntracellular Signaling Peptides and ProteinsN4-(2,2-dimethyl-3-oxo-4H-pyrid(1,4)oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamineNiacinamideOxazinesProtein Kinase InhibitorsProtein-Tyrosine KinasesPyridinesPyrimidinesReceptors, IgERNA, Small InterferingSyk KinaseSYK protein, humanSyk protein, mouseSyk protein, ratTumor Necrosis Factor-alpha

Identifiers

PMID20053395
PMCPMC7124319
OpenAlexW2038842078

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.