Evidence map›Paper›PMID 28273337›Full record

ArticleAlcoholism, clinical and experimental research2017

Ethanol, TLR3, and TLR4 Agonists Have Unique Innate Immune Responses in Neuron-Like SH-SY5Y and Microglia-Like BV2.

Colleen J Lawrimore, Fulton T Crews

Open access · hybridAbstract read
In one paragraph

Article in Alcoholism, clinical and experimental research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
4.6field-weighted citation impact, top 5% 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

47 citing papers in PubMed, 69 citations in OpenAlex.

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  9. Alcohol, HMGB1, and Innate Immune Signaling in the Brain.Alcohol research : current reviews · 2024
    Review
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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

2 authors at 1 institution in 1 country.

Colleen J LawrimoreBowles Center for Alcohol Studies , School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.ORCID http://orcid.org/0000-0002-0135-1406
Fulton T CrewsBowles Center for Alcohol Studies , School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
University of North Carolina at Chapel Hill · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
UNC ARC Information/Dissemination CoreP60AA011605 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Melissa A Herman · 2003 to 2026
$46.3M
Supplement to Molecular and Cellular Studies on Alcohol's ActionsT32AA007573 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FULTON T CREWS, Thomas L. Kash · 1997 to 2026
$9.3M
UNC-CH NADIA Underage Drinking and Adult Brain Morphology in RatsU01AA020023 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CREWS, FULTON T · 2010 to 2024
$7.5M
UNC-CH NADIA Administrative CoreU24AA020024 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CREWS, FULTON T · 2010 to 2024
$6.6M
MOLECULAR AND CELLULAR PATHOGENESIS IN ALCOHOLISMP50AA011605 · NIAAA · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · PI CREWS, FULTON T · 1998 to 2002
$4.9M
Pregnane X receptor (PRX)-dependent mechanisms of alcoholic liver diseaseU54AA019767 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CREWS, FULTON T · 2010 to 2019
$2.1M
Adult neurobiology following adolescent drinkingF32AA021040 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI VETRENO, RYAN PETER · 2012 to 2013
$101k
NCI NIH HHS P30 CA016086NIAAA NIH HHS F32 AA021040NIAAA NIH HHS P50 AA011605NIAAA NIH HHS P60 AA011605NIAAA NIH HHS T32 AA007573NIAAA NIH HHS U01 AA020023NIAAA NIH HHS U24 AA020024NIAAA NIH HHS U54 AA019767
6 · The paper itself

Abstract

backgroundEthanol (EtOH) consumption leads to an increase of proinflammatory signaling via activation of Toll-like receptors (TLRs) such as TLR3 and TLR4 that leads to kinase activation (ERK1/2, p38, TBK1), transcription factor activation (NFκB, IRF3), and increased transcription of proinflammatory cytokines such as TNF-α, IL-1β, and IL-6. This immune signaling cascade is thought to play a role in neurodegeneration and alcohol use disorders. While microglia are considered to be the primary macrophage in brain, it is unclear what if any role neurons play in EtOH-induced proinflammatory signaling.

methodsMicroglia-like BV2 and retinoic acid-differentiated neuron-like SH-SY5Y were treated with TLR3 agonist Poly(I:C), TLR4 agonist lipopolysaccharide (LPS), or EtOH for 10 or 30 minutes to examine proinflammatory immune signaling kinase and transcription factor activation using Western blot, and for 24 hours to examine induction of proinflammatory gene mRNA using RT-PCR.

resultsIn BV2, both LPS and Poly(I:C) increased p-ERK1/2, p-p38, and p-NFκB by 30 minutes, whereas EtOH decreased p-ERK1/2 and increased p-IRF3. LPS, Poly(I:C), and EtOH all increased TNF-α and IL-1β mRNA, and EtOH further increased TLR2, 7, 8, and MD-2 mRNA in BV2. In SH-SY5Y, LPS had no effect on kinase or proinflammatory gene expression. However, Poly(I:C) increased p-p38 and p-IRF3, and increased expression of TNF-α, IL-1β, and IL-6, while EtOH increased p-p38, p-IRF3, p-TBK1, and p-NFκB while decreasing p-ERK1/2 and increasing expression of TLR3, 7, 8, and RAGE mRNA. HMGB1, a TLR agonist, was induced by LPS in BV2 and by EtOH in both cell types. EtOH was more potent at inducing proinflammatory gene mRNA in SH-SY5Y compared with BV2.

conclusionsThese results support a novel and unique mechanism of EtOH, TLR3, and TLR4 signaling in neuron-like SH-SY5Y and microglia-like BV2 that likely contributes to the complexity of brain neuroimmune signaling.

Indexed as

AnimalsCell Line, TumorDose-Response Relationship, DrugEthanolHumansImmunity, InnateMiceMicrogliaNeuronsPoly I-CToll-Like Receptor 3Toll-Like Receptor 4EthanolPoly I-CTLR3 protein, humanToll-Like Receptor 3Toll-Like Receptor 4EthanolInnate ImmuneMicrogliaNeuronToll-Like Receptor

Identifiers

PMID28273337
PMCPMC5407472
OpenAlexW2593911670

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.