Evidence map›Paper›PMID 30103265›Full record

ArticleAlcoholism, clinical and experimental research2018

TLR7-let-7 Signaling Contributes to Ethanol-Induced Hepatic Inflammatory Response in Mice and in Alcoholic Hepatitis.

Veronica L Massey, Liya Qin, Joaquin Cabezas, Juan Caballeria, Pau Sancho-Bru, Ramon Bataller, Fulton T Crews

Open access · hybridAbstract read
In one paragraph

Article in Alcoholism, clinical and experimental research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

19 citing papers in PubMed, 34 citations in OpenAlex.

  1. miRNAs and Alcohol-Related Hepatitis.Current issues in molecular biology · 2025
    Review
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  5. The miR-29-3p family suppresses inflammatory osteolysis.Journal of cellular physiology · 2024
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  16. Triterpenoids Extracted FromFrontiers in microbiology · 2020
    Article
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  18. Article
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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

7 authors at 4 institutions in 2 countries.

Veronica L MasseyBowles Center for Alcohol Studies, University of North Carolina Medical School, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Liya QinBowles Center for Alcohol Studies, University of North Carolina Medical School, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Joaquin CabezasGastroenterology and Hepatology, Hospital Marques de Valdecilla, Research Institute Valdecilla, Santander, Spain.
Juan CaballeriaInstitut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Catalonia, Spain.
Pau Sancho-BruInstitut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Catalonia, Spain.
Ramon BatallerBowles Center for Alcohol Studies, University of North Carolina Medical School, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Fulton T CrewsBowles Center for Alcohol Studies, University of North Carolina Medical School, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.ORCID 0000-0003-2393-4976
University of North Carolina at Chapel Hill · USCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas · ESHospital Clínic de Barcelona · ESMarqués de Valdecilla University Hospital · ES

Funding

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 Subtypes for Targeted Therapies in Alcoholic HepatitisU01AA021908 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BATALLER, RAMON · 2013 to 2017
$6.0M
MOLECULAR AND CELLULAR PATHOGENESIS IN ALCOHOLISMP50AA011605 · NIAAA · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · PI CREWS, FULTON T · 1998 to 2002
$4.9M
UNC-CH NADIA Scientific CoreU24AA020022 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CREWS, FULTON T · 2010 to 2014
$2.2M
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
Alcohol and Development of the Prefrontal CortexF30AA018051 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI COLEMAN, LEON GARLAND · 2008 to 2011
$119k
NIAAA NIH HHS 1U01AA021908-01NIAAA NIH HHS AA018051NIAAA NIH HHS F30 AA018051NIAAA NIH HHS P50 AA011605NIAAA NIH HHS P60 AA011605NIAAA NIH HHS T32 AA007573NIAAA NIH HHS U01 AA020023NIAAA NIH HHS U01 AA021908NIAAA NIH HHS U24 AA020022NIAAA NIH HHS U24 AA020024NIAAA NIH HHS U54 AA019767UNC Bowles Center for Alcohol Studies
6 · The paper itself

Abstract

backgroundToll-like receptor 7 (TLR7) is an endosomal TLR that is activated by single-stranded RNA, including endogenous microRNAs (e.g., let-7b). Increased hepatic expression of TLRs, microRNAs, and inflammatory mediators is linked to ethanol (EtOH) exposure and to alcoholic liver disease (ALD). ALD invovles chronic hepatic inflammation that can progress to alcoholic hepatitis (AH), a particularly severe form of ALD. This study aimed to investigate TLR7 expression in patients with different liver disease phenotypes and in mouse liver following alcohol exposure.

methodsHepatic mRNA expression was determined by RNA sequencing of liver tissue from patients with liver disease or normal liver tissue. Mice were exposed to subchronic EtOH followed by administration of the TLR7 agonist imiquimod. Primary human hepatocytes were exposed to EtOH or imiquimod in vitro.

resultsRNAseq analysis revealed that hepatic expression of TLR7 and let-7b microRNA, an endogenous TLR7 ligand, was significantly increased in AH patients. Hepatic expression of TLR7 and let-7b positively correlated with hepatic IL-8 mRNA expression. In mice, EtOH increased hepatic TLR7 mRNA expression and enhanced imiquimod-induced expression of the pro-inflammatory mediators TNFα, MCP-1, and iNOS. In vitro, EtOH significantly increased hepatocyte TLR7 mRNA and the TLR7 agonist, imiquimod, induced hepatocyte expression of TNFα and IL-8 mRNA. EtOH also increased the release of let-7b in microvesicles from hepatocytes, suggesting that EtOH can increase the expression of both the receptor and its endogenous ligand.

conclusionsThese studies suggest that increased TLR7 signaling caused by increased expression of TLR7 and its endogenous ligand let-7b may contribute to the enhanced inflammatory response associated with AH.

Indexed as

AdultAgedAnimalsCentral Nervous System DepressantsCytokinesEthanolFemaleHepatitis, AlcoholicHepatocytesHumansImiquimodInflammationInterleukin-8LiverMaleMembrane GlycoproteinsCentral Nervous System DepressantsCytokinesEthanolImiquimodInterleukin-8Membrane GlycoproteinsMicroRNAsRNA, MessengerTlr7 protein, mouseToll-Like Receptor 7HepatocyteHumanLiver DiseasemicroRNAPro-Inflammatory Cytokines

Identifiers

PMID30103265
PMCPMC6282707
OpenAlexW2887917093

What OpenQuestion holds

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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.