Evidence map›Paper›PMID 19428336›Full record

ArticleBiochemical pharmacology2009

Cromoglycate drugs suppress eicosanoid generation in U937 cells by promoting the release of Anx-A1.

Samia Yazid, Egle Solito, Helen Christian, Simon McArthur, Nicolas Goulding, Roderick Flower

Open access · hybridAbstract read
In one paragraph

Article in Biochemical pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.

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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

6 authors at 3 institutions in 1 country.

Samia YazidBiochemical Pharmacology, William Harvey Research Institute, Bart's and the London School of Medicine and Dentistry, London, UK.
Egle Solito
Helen Christian
Simon McArthur
Nicolas Goulding
Roderick Flower
Imperial College London · GBWilliam Harvey Research Institute · GBUniversity of Oxford · GB

Funding

Wellcome Trust N072634/Z/08/Z
6 · The paper itself

Abstract

Using biochemical, epifluorescence and electron microscopic techniques in a U937 model system, we investigated the effect of anti-allergic drugs di-sodium cromoglycate and sodium nedocromil on the trafficking and release of the anti-inflammatory protein Annexin-A1 (Anx-A1) when this was triggered by glucocorticoid (GC) treatment. GCs alone produced a rapid (within 5min) concentration-dependent activation of PKCalpha/beta (Protein Kinase C; EC 2.7.11.13) and phosphorylation of Anx-A1 on Ser(27). Both phosphoproteins accumulated at the plasma membrane and Anx-A1 was subsequently externalised thereby inhibiting thromboxane (Tx) B(2) generation. When administered alone, cromoglycate or nedocromil had little effect on this pathway however, in the presence of a fixed sub-maximal concentration of GCs, increasing amounts of the cromoglycate-like drugs caused a striking concentration-dependent enhancement of Anx-A1 and PKCalpha/beta phosphorylation, membrane recruitment and Anx-A1 release from cells resulting in greatly enhanced inhibition of TxB(2) generation. GCs also stimulated phosphatase accumulation at the plasma membrane of U937 cells. Both cromoglycate and nedocromil inhibited this enzymatic activity as well as that of a highly purified PP2A phosphatase preparation. We conclude that stimulation by the cromoglycate-like drugs of intracellular Anx-A1 trafficking and release (hence inhibition of eicosanoid release) is secondary to inhibition of a phosphatase PP2A (phosphoprotein phosphatase; EC 3.1.3.16), which probably forms part of a control loop to limit Anx-A1 release. These experiments provide a basis for a novel mechanism of action for the cromolyns, a group of drugs that have long puzzled investigators.

Indexed as

Annexin A1Anti-Asthmatic AgentsCromolyn SodiumDrug Therapy, CombinationEicosanoidsGlucocorticoidsHumansNedocromilProtein Kinase CProtein Phosphatase 2Protein TransportU937 CellsAnnexin A1Anti-Asthmatic AgentsCromolyn SodiumEicosanoidsGlucocorticoidsNedocromilProtein Kinase CProtein Phosphatase 2

Identifiers

PMID19428336
PMCPMC2888050
OpenAlexW1981762108

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.