Evidence map›Paper›PMID 26701099›Full record

ArticleJournal of biomolecular screening2016

Focused Screening Identifies Evoxine as a Small Molecule That Counteracts CO2-Induced Immune Suppression.

Iiro Taneli Helenius, Aisha Nair, Humberto E Trejo Bittar, Jacob I Sznajder, Peter H S Sporn, Greg J Beitel

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of biomolecular screening, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.5field-weighted citation impact, top 28% 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

0 citing papers in PubMed, 4 citations in OpenAlex.

No citing paper in PubMed yet.

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 2 institutions in 1 country.

Iiro Taneli HeleniusDepartment of Molecular Biosciences, Northwestern University, Evanston, IL, USA Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA, USA.
Aisha NairDivision of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Humberto E Trejo BittarDivision of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Jacob I SznajderDivision of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Peter H S SpornDivision of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA.
Greg J BeitelDepartment of Molecular Biosciences, Northwestern University, Evanston, IL, USA beitel@northwestern.edu.
Northwestern University · USJesse Brown VA Medical Center · US

Funding

Treatments for Nipah Virus InfectionU54AI057159 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI KASPER, DENNIS L. · 2003 to 2013
$113.7M
New collections of dsRNAs and overexpression miRNA constructs to supplement RNAiR01GM067761 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI PERRIMON, NORBERT · 2003 to 2019
$15.5M
The injurious effects of hypercapnia on the alveolar epitheliumR01HL085534 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI SZNAJDER, JACOB I · 2006 to 2018
$4.9M
Role and Regulation of Sodium, Potasium ATPase in LungR37HL048129 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI SZNAJDER, JACOB I · 2008 to 2017
$4.0M
Genes Mediating Innate Immune Suppression by Hypercapnia in Mammals and FliesR01HL107629 · NHLBI · NORTHWESTERN UNIVERSITY · PI BEITEL, GREG J, SPORN, PETER H · 2012 to 2015
$1.5M
NHLBI NIH HHS R01 HL085534NHLBI NIH HHS R01 HL107629NHLBI NIH HHS R01-HL107629NHLBI NIH HHS R01-HL-85534NHLBI NIH HHS R37 HL048129NIAID NIH HHS U54 AI057159NIAID NIH HHS U54-AI057159NIGMS NIH HHS R01 GM067761NIGMS NIH HHS R01-GM067761
6 · The paper itself

Abstract

Patients with severe lung disease may develop hypercapnia, elevation of the levels of CO2 in the lungs and blood, which is associated with increased risk of death, often from infection. To identify compounds that ameliorate the adverse effects of hypercapnia, we performed a focused screen of 8832 compounds using a CO2-responsive luciferase reporter in Drosophila S2* cells. We found that evoxine, a plant alkaloid, counteracts the CO2-induced transcriptional suppression of antimicrobial peptides in S2* cells. Strikingly, evoxine also inhibits hypercapnic suppression of interleukin-6 and the chemokine CCL2 expression in human THP-1 macrophages. Evoxine's effects are selective, since it does not prevent hypercapnic inhibition of phagocytosis by THP-1 cells or CO2-induced activation of AMPK in rat ATII pulmonary epithelial cells. The results suggest that hypercapnia suppresses innate immune gene expression by definable pathways that are evolutionarily conserved and demonstrate for the first time that specific CO2 effects can be targeted pharmacologically.

Indexed as

High-Throughput Screening AssaysAlkaloidsAnimalsAntimicrobial Cationic PeptidesCarbon DioxideCell LineChemokine CCL2Drosophila melanogasterEpithelial CellsGene ExpressionGenes, ReporterHumansHypercapniaInterleukin-6LuciferasesMacrophagesAlkaloidsAntimicrobial Cationic PeptidesCarbon DioxideCCL2 protein, humanChemokine CCL2IL6 protein, humanInterleukin-6Luciferasesanti-infective drugscell-based assaysimmune system diseasesreporter gene assays

Identifiers

PMID26701099
PMCPMC5096368
OpenAlexW2303594520

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.