Evidence map›Paper›PMID 31899206›Full record

ArticleJournal of hepatology2020

IL-17 signaling in steatotic hepatocytes and macrophages promotes hepatocellular carcinoma in alcohol-related liver disease.

Hsiao-Yen Ma, Gen Yamamoto, Jun Xu, Xiao Liu, Daniel Karin, Ju Youn Kim, Ludmil B Alexandrov, Yukinori Koyama, Takahiro Nishio, Chris Benner and 16 more

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

Article in Journal of hepatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
138citing papers in PubMed, 1 pooled it
11.0field-weighted citation impact, top 1% 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

138 citing papers in PubMed, 1 synthesis or guideline pooled it, 198 citations in OpenAlex.

  1. A Review of CXCL1 in Cardiac Fibrosis.Frontiers in cardiovascular medicine · 2021
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78 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors at 5 institutions in 2 countries.

Hsiao-Yen MaDepartment of Medicine, University of California San Diego, La Jolla, CA, USA; Department of Surgery, University of California San Diego, La Jolla, CA, USA.
Gen YamamotoDepartment of Medicine, University of California San Diego, La Jolla, CA, USA; Department of Surgery, University of California San Diego, La Jolla, CA, USA.
Jun XuDepartment of Medicine, University of California San Diego, La Jolla, CA, USA; Department of Surgery, University of California San Diego, La Jolla, CA, USA.
Xiao LiuDepartment of Medicine, University of California San Diego, La Jolla, CA, USA; Department of Surgery, University of California San Diego, La Jolla, CA, USA.
Daniel KarinDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Ju Youn KimDepartment of Pharmacology, University of California San Diego, La Jolla, CA, USA.
Ludmil B AlexandrovDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Yukinori KoyamaDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Takahiro NishioDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Chris BennerDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Sven HeinzDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Sara B RosenthalDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Shuang LiangDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Mengxi SunDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Gabriel KarinDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Peng ZhaoDepartment of Pharmacology, University of California San Diego, La Jolla, CA, USA.
Pnina BrodtDepartment of Medicine, McGill University and the McGill University Health Center, Montreal, QC, Canada.
Iain H MckillopDepartment of Biology, University of North Carolina at Charlotte, Charlotte, NC, USA.
Oswald QuehenbergerDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Ed DennisDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Alan SaltielDepartment of Pharmacology, University of California San Diego, La Jolla, CA, USA.
Hidekazu TsukamotoSouthern California Research Center for ALPD and Cirrhosis, Department of Pathology, Keck School of Medicine of USC, Los Angeles, CA, USA; Department of Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
Bin GaoLaboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
Michael KarinDepartment of Pharmacology, University of California San Diego, La Jolla, CA, USA.
David A BrennerDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Tatiana KisselevaDepartment of Surgery, University of California San Diego, La Jolla, CA, USA. Electronic address: tkisseleva@ucsd.edu.
University of California San Diego · USMcGill University Health Centre · CANational Institutes of Health · USSouthern California Reproductive Center · USUniversity of North Carolina at Charlotte · US

Funding

Yeast Genetics and Stress Response Genes-BiomedicalP42ES010337 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TUKEY, ROBERT H · 2000 to 2022
$69.8M
The Southernearch Center for ALPD and CirrhosisP50AA011999 · NIAAA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ANNA S. GUKOVSKAYA · 1999 to 2026
$45.8M
REGULATION OF NFKB AND IKK BY PROINFLAMMATORY STIMULIR01AI043477 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KARIN, MICHAEL · 1998 to 2017
$7.4M
NF-kappaB and Mitochondrial Signals as Positive and Negative Regulators of InflammationR37AI043477 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Michael Karin · 2018 to 2026
$6.0M
Inactivation of Hepatic Stellate Cells During Reversal of Liver FibrosisR01DK099205 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BRENNER, DAVID A., KISSELEVA, TATIANA · 2014 to 2025
$4.8M
Control of Lipogenesis and Hepatic Steatosis by Caspase-2R01DK120714 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Michael Karin · 2019 to 2026
$4.0M
The Role of Portal Fibroblasts in Cholestatic Liver FibrosisR01DK101737 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KISSELEVA, TATIANA · 2014 to 2025
$3.8M
Novel IL-23 inhibitor for the treatment of alcohol associated liver diseaseU01AA029019 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KISSELEVA, TATIANA, LOOMBA, ROHIT · 2020 to 2024
$3.7M
Epigenetic Regulation of Alcoholic Liver FibrosisU01AA018663 · NIAAA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI KISSELEVA, TATIANA, MANN, DEREK · 2010 to 2019
$3.7M
Immunosuppressive mechanisms responsible for development of non-viral liver cancer and control of its response to immune checkpoint inhibitorsU01AA027681 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI EL-KHOUEIRY, ANTHONY BOUTROS, KARIN, MICHAEL · 2018 to 2022
$3.6M
Role of p62/SQSTM1 in obesity-induced liver cancerR01CA211794 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KARIN, MICHAEL, MOSCAT, JORGE · 2017 to 2021
$3.6M
Highly penetrant and immunogenic mouse models of non-viral HCC that are suitable for evaluation of immune checkpoint inhibitorsR01CA234128 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KARIN, MICHAEL · 2019 to 2023
$2.7M
NCI NIH HHS R01 CA211794NCI NIH HHS R01 CA234128NIAAA NIH HHS P50 AA011999NIAAA NIH HHS R01 AA028550NIAAA NIH HHS U01 AA018663NIAAA NIH HHS U01 AA022614NIAAA NIH HHS U01 AA027681NIAAA NIH HHS U01 AA029019NIAID NIH HHS R01 AI043477NIAID NIH HHS R37 AI043477NIDDK NIH HHS R01 DK099205NIDDK NIH HHS R01 DK101737NIDDK NIH HHS R01 DK111866NIDDK NIH HHS R01 DK120714NIDDK NIH HHS R56 DK088837NIEHS NIH HHS P42 ES010337
6 · The paper itself

Abstract

BACKGROUND &

aimsChronic alcohol consumption is a leading risk factor for the development of hepatocellular carcinoma (HCC), which is associated with a marked increase in hepatic expression of pro-inflammatory IL-17A and its receptor IL-17RA.

methodsGenetic deletion and pharmacological blocking were used to characterize the role of IL-17A/IL-17RA signaling in the pathogenesis of HCC in mouse models and human specimens.

resultsWe demonstrate that the global deletion of the Il-17ra gene suppressed HCC in alcohol-fed diethylnitrosamine-challenged Il-17ra

conclusionsOverall, IL-17A is a tumor-promoting cytokine, which critically regulates alcohol-induced hepatic steatosis, inflammation, fibrosis, and HCC. LAY SUMMARY: IL-17A is a tumor-promoting cytokine, which critically regulates inflammatory responses in macrophages (Kupffer cells and bone-marrow-derived monocytes) and cholesterol synthesis in steatotic hepatocytes in an experimental model of alcohol-induced HCC. Therefore, IL-17A may be a potential therapeutic target for patients with alcohol-induced HCC.

Indexed as

AnimalsCarcinogenesisCarcinoma, HepatocellularDisease Models, AnimalEthanolGene DeletionHepatocytesHumansInterleukin-17Kupffer CellsLiver CirrhosisLiver Diseases, AlcoholicLiver NeoplasmsMaleMiceMice, Inbred C57BLEthanolIL17A protein, humanIl17a protein, mouseIl17ra protein, mouseInterleukin-17Receptors, Interleukin-17Alcoholic liver diseaseALDCholesterol synthesisFibrosisHCCHepatocellular carcinomaIL-17 signalingInflammationMutational signatures

Identifiers

PMID31899206
PMCPMC7167339
OpenAlexW2996882089

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.