Evidence map›Paper›PMID 26640957›Full record

ArticlePloS one2015

Comparison of Gene Expression by Sheep and Human Blood Stimulated with the TLR4 Agonists Lipopolysaccharide and Monophosphoryl Lipid A.

Perenlei Enkhbaatar, Christina Nelson, John R Salsbury, Joseph R Carmical, Karen E O Torres, David Herndon, Donald S Prough, Liming Luan, Edward R Sherwood

Open access · goldAbstract readComparative Study
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

23 citing papers in PubMed, 37 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

9 authors at 5 institutions in 1 country.

Perenlei EnkhbaatarDepartment of Anesthesiology, the University of Texas Medical Branch, Galveston, TX, United States of America.
Christina NelsonDepartment of Anesthesiology, the University of Texas Medical Branch, Galveston, TX, United States of America.
John R SalsburyDepartment of Anesthesiology, the University of Texas Medical Branch, Galveston, TX, United States of America.
Joseph R CarmicalMolecular Virology and Microbiology Core, Alkek Center for Metagenomics & Microbiome Research, Baylor College of Medicine, Houston, TX, United States of America.
Karen E O TorresGenUs BioSystems, Northbrook, IL, United States of America.
David HerndonShriners Hospital for Children, Galveston, TX, United States of America.
Donald S ProughDepartment of Anesthesiology, the University of Texas Medical Branch, Galveston, TX, United States of America.
Liming LuanDepartment of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, United States of America.
Edward R SherwoodDepartment of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, United States of America.
The University of Texas Medical Branch at Galveston · USVanderbilt University Medical Center · USBaylor College of Medicine · USGenUs BioSystems (United States) · USShriners Hospitals for Children - Galveston · US

Funding

Etiology of Microvascular Changes in Gram-positive Sepsis: Mechanisms and Therapeutic OptionsR01GM097480 · NIGMS · UNIVERSITY OF TEXAS MED BR GALVESTON · PI ENKHBAATAR, PERENLEI · 2012 to 2022
$2.7M
Augmentation of Innate Anti-Microbial Immunity by TLR4 AgonistsR01GM104306 · NIGMS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ENKHBAATAR, PERENLEI, SHERWOOD, EDWARD R · 2013 to 2016
$1.2M
NIGMS NIH HHS GM097480NIGMS NIH HHS GM104306NIGMS NIH HHS R01 GM097480NIGMS NIH HHS R01 GM104306
6 · The paper itself

Abstract

backgroundAnimal models that mimic human biology are important for successful translation of basic science discoveries into the clinical practice. Recent studies in rodents have demonstrated the efficacy of TLR4 agonists as immunomodulators in models of infection. However, rodent models have been criticized for not mimicking important characteristics of the human immune response to microbial products. The goal of this study was to compare genomic responses of human and sheep blood to the TLR4 agonists lipopolysaccharide (LPS) and monophosphoryl lipid A (MPLA).

methodsVenous blood, withdrawn from six healthy human adult volunteers (~ 28 years old) and six healthy adult female sheep (~3 years old), was mixed with 30 μL of PBS, LPS (1μg/mL) or MPLA (10μg/mL) and incubated at room temperature for 90 minutes on a rolling rocker. After incubation, 2.5 mL of blood was transferred to Paxgene Blood RNA tubes. Gene expression analysis was performed using an Agilent Bioanalyzer with the RNA6000 Nano Lab Chip. Agilent gene expression microarrays were scanned with a G2565 Microarray Scanner. Differentially expressed genes were identified.

results11,431 human and 4,992 sheep probes were detected above background. Among them 1,029 human and 175 sheep genes were differentially expressed at a stringency of 1.5-fold change (p<0.05). Of the 175 sheep genes, 54 had a known human orthologue. Among those genes, 22 had > 1.5-fold changes in human samples. Genes of major inflammatory mediators, such as IL-1, IL-6 and IL-8, TNF alpha, NF-kappaB, ETS2, PTGS2, PTX3, CXCL16, KYNU, and CLEC4E were similarly (>2-fold) upregulated by LPS and MPLA in both species.

conclusionThe genomic responses of peripheral blood to LPS and MPLA in sheep are quite similar to those observed in humans, supporting the use of the ovine model for translational studies that mimic human inflammatory diseases and the study of TLR-based immunomodulators.

Indexed as

AdultAnimalsBloodFemaleFluorescenceGene Expression RegulationHigh-Throughput Nucleotide SequencingHumansLipid ALipopolysaccharidesSheepSpecies SpecificityToll-Like Receptor 4Lipid ALipopolysaccharidesmonophosphoryl lipid ATLR4 protein, humanToll-Like Receptor 4

Identifiers

PMID26640957
PMCPMC4671644
OpenAlexW2278214458

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.