Evidence map›Paper›PMID 25930080›Full record

ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2015

TLR2 and TLR9 contribute to alcohol-mediated liver injury through induction of CXCL1 and neutrophil infiltration.

Yoon Seok Roh, Bi Zhang, Rohit Loomba, Ekihiro Seki

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

Article in American journal of physiology. Gastrointestinal and liver physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed
7.5field-weighted citation impact, top 2% 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

88 citing papers in PubMed, 138 citations in OpenAlex.

  1. Ethanol reshapes FFC-driven steatohepatitis through time-dependent fibrosis and lipid-droplet remodeling.American journal of physiology. Gastrointestinal and liver physiology · 2026
    Article
  2. [Alcohol liver disease: immunoregulatory mechanisms and precision therapeutic targets].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026
    Review
  3. Antimicrobial Peptide CPP-C3M4 AttenuatesAnimals : an open access journal from MDPI · 2026
    Article
  4. Review
  5. Article
  6. Neutrophil-T cell cross talk in noninfectious liver diseases.American journal of physiology. Gastrointestinal and liver physiology · 2026
    Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Microorganisms · 2025
    Article
  13. Article
  14. Article
  15. Review
  16. Review
  17. Review
  18. Review
  19. Review
  20. Article

28 more citing papers are in PubMed but not listed here.

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

4 authors at 2 institutions in 1 country.

Yoon Seok RohDivision of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California; and Division of Gastroenterology, Department of Medicine, University of California, San Diego, School of Medicine, La Jolla, California.
Bi ZhangDivision of Gastroenterology, Department of Medicine, University of California, San Diego, School of Medicine, La Jolla, California.
Rohit LoombaDivision of Gastroenterology, Department of Medicine, University of California, San Diego, School of Medicine, La Jolla, California.
Ekihiro SekiDivision of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California; and Division of Gastroenterology, Department of Medicine, University of California, San Diego, School of Medicine, La Jolla, California ekihiro.seki@cshs.org.
Cedars-Sinai Medical Center · USUniversity of California, San Diego · US

Funding

LPS binding to TLR4 regulates hepatic stellate cell activation and fibrosisR01DK085252 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI EKIHIRO SEKI · 2011 to 2026
$4.8M
Synergistic Actions By Multiple Toll-Like Receptors in Alcoholic Liver DiseaseR01AA020172 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SEKI, EKIHIRO · 2010 to 2014
$1.8M
GENETIC EPIDEMIOLOGY OF NONALCOHOLIC FATTY LIVER DISEASEK23DK090303 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LOOMBA, ROHIT · 2011 to 2014
$721k
NIAAA NIH HHS R01 AA020172NIAAA NIH HHS R01AA02172NIDDK NIH HHS K23-DK090303NIDDK NIH HHS R01 DK085252NIDDK NIH HHS R01DK085252
6 · The paper itself

Abstract

Although previous studies reported the involvement of the TLR4-TRIF pathway in alcohol-induced liver injury, the role of TLR2 and TLR9 signaling in alcohol-mediated neutrophil infiltration and liver injury has not been elucidated. Since alcohol binge drinking is recognized to induce more severe form of alcohol liver disease, we used a chronic-binge ethanol-feeding model as a mouse model for early stage of alcoholic hepatitis. Whereas a chronic-binge ethanol feeding induced alcohol-mediated liver injury in wild-type mice, TLR2- and TLR9-deficient mice showed reduced liver injury. Induction of neutrophil-recruiting chemokines, including Cxcl1, Cxcl2, and Cxcl5, and hepatic neutrophil infiltration were increased in wild-type mice, but not in TLR2- and TLR9-deficient mice. In vivo depletion of Kupffer cells (KCs) by liposomal clodronate reduced liver injury and the expression of Il1b, but not Cxcl1, Cxcl2, and Cxcl5, suggesting that KCs are partly associated with liver injury, but not neutrophil recruitment, in a chronic-binge ethanol-feeding model. Notably, hepatocytes and hepatic stellate cells (HSCs) produce high amounts of CXCL1 in ethanol-treated mice. The treatment with TLR2 and TLR9 ligands synergistically upregulated CXCL1 expression in hepatocytes. Moreover, the inhibitors for CXCR2, a receptor for CXCL1, and MyD88 suppressed neutrophil infiltration and liver injury induced by chronic-binge ethanol treatment. Consistent with the above findings, hepatic CXCL1 expression was highly upregulated in patients with alcoholic hepatitis. In a chronic-binge ethanol-feeding model, the TLR2 and TLR9-dependent MyD88-dependent pathway mediates CXCL1 production in hepatocytes and HSCs; the CXCL1 then promotes neutrophil infiltration into the liver via CXCR2, resulting in the development of alcohol-mediated liver injury.

Indexed as

Neutrophil InfiltrationAnimalsBinge DrinkingCells, CulturedChemokine CXCL1Disease Models, AnimalEthanolFemaleHepatic Stellate CellsHepatocytesKupffer CellsLiverLiver Diseases, AlcoholicMice, Inbred C57BLMice, KnockoutMyeloid Differentiation Factor 88Chemokine CXCL1CXCL1 protein, humanCxcl1 protein, mouseEthanolMyd88 protein, mouseMyeloid Differentiation Factor 88Receptors, Interleukin-8BTlr2 protein, mouseTlr9 protein, mouseToll-Like Receptor 2Toll-Like Receptor 9AHALDbinge ethanol feedingchemokineMyD88

Identifiers

PMID25930080
PMCPMC4491507
OpenAlexW1974216719

What OpenQuestion holds

Textmetadata
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.