Evidence map›Paper›PMID 31129422›Full record

ArticleInternational immunopharmacology2019

Pharmacological stimulation of G-protein coupled receptor 40 alleviates cytokine-induced epithelial barrier disruption in airway epithelial Calu-3 cells.

Aekkacha Moonwiriyakit, Michael Koval, Chatchai Muanprasat

Open access · greenAbstract read
In one paragraph

Article in International immunopharmacology, 2019. 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
0.8field-weighted citation impact, top 27% 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, 17 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

3 authors at 2 institutions in 2 countries.

Aekkacha MoonwiriyakitDepartment of Physiology, Faculty of Science, Mahidol University, Rama VI Road, Rajathevi, Bangkok 10400, Thailand.
Michael KovalDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia.
Chatchai MuanprasatDepartment of Physiology, Faculty of Science, Mahidol University, Rama VI Road, Rajathevi, Bangkok 10400, Thailand; Excellent Center for Drug Discovery (ECDD), Mahidol University, Rama VI Road, Rajathevi, Bangkok 10400, Thailand; Research Center of Transport Proteins for Medical Innovation, Faculty of Science, Mahidol University, Rama VI Road, Rajathevi, Bangkok 10400, Thailand. Electronic address: chatchai.mua@mahidol.ac.th.
Mahidol University · THEmory University · US

Funding

Alcohol and the alveolar epithelial barrierR01AA025854 · NIAAA · EMORY UNIVERSITY · PI KOVAL, MICHAEL H. · 2017 to 2021
$1.9M
NIAAA NIH HHS R01 AA025854
6 · The paper itself

Abstract

Impairment of airway tight junctions induced by elevated levels of proinflammatory cytokines is implicated in the pathogenesis of inflammatory airway diseases. Pharmacological stimulation of G-protein coupled receptor (GPR) 40, a receptor of polyunsaturated fatty acids, have recently been shown to promote tight junction assembly in airway epithelial cells under non-inflammatory conditions. However, roles of GPR40 in regulating airway epithelial integrity in response to inflammatory insults are unknown. This study was aimed to investigate the effect of GPR40 stimulation on proinflammatory cytokine (TNFα and IL-1β)-induced tight junction disruption in human airway epithelial Calu-3 cells using GW9508, a GPR40 agonist. We found that stimulation of GPR40 by GW9508 attenuated the cytokine-induced airway epithelial barrier leakage as analyzed by measurements of transepithelial electrical resistance and transepithelial flux of fluorescently labeled dextran (molecular weight of 4 kDa). Furthermore, GW9508 prevented the cytokine-induced dislocalization of zonula occludens (ZO)-1, occludin and claudin-1. The barrier-protective effect of GW9508 was abolished by a GPR40 antagonist, but not a GPR120 antagonist. Immunofluorescence staining of NF-ĸB indicated that GW9508 had no effect on cytokine-induced NF-ĸB activation. Intriguingly, GW9508 inhibited cytokine-induced airway epithelial barrier disruption through suppression of extracellular signal-regulated kinase (ERK) phosphorylation in a phospholipase C (PLC) and calcium/calmodulin-dependent protein kinase kinase beta (CaMKKβ)-dependent manner. Collectively, this study uncovered the novel role of GPR40 in preventing cytokine-induced tight junction disruption in airway epithelial cells through mechanisms involving PLC-CaMKKβ-mediated suppression of ERK signaling. Pharmacological stimulation of GPR40 may be beneficial in the treatment of airway diseases.

Indexed as

Calcium-Calmodulin-Dependent Protein Kinase KinaseCell LineCytokinesEpithelial CellsExtracellular Signal-Regulated MAP KinasesHumansMethylaminesPropionatesReceptors, G-Protein-CoupledSignal TransductionTight JunctionsType C PhospholipasesCalcium-Calmodulin-Dependent Protein Kinase KinaseCytokinesExtracellular Signal-Regulated MAP KinasesFFAR1 protein, humanGW9508MethylaminesPropionatesReceptors, G-Protein-CoupledType C PhospholipasesAirway epithelial cellsCOPDERKGPR40IL–1βTight junctionsTNFα

Identifiers

PMID31129422
PMCPMC6620115
OpenAlexW2945532440

What OpenQuestion holds

Textmetadata
LicenceTDM
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.