Evidence map›Paper›PMID 25063867›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2014

Acute and chronic effects of IL-22 on acetaminophen-induced liver injury.

Dechun Feng, Yan Wang, Hua Wang, Honglei Weng, Xiaoni Kong, Brittany V Martin-Murphy, Yongmei Li, Ogyi Park, Steven Dooley, Cynthia Ju and 1 more

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

Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
6.9field-weighted citation impact, top 3% 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

44 citing papers in PubMed, 62 citations in OpenAlex.

  1. Novel treatment of acute and acute-on-chronic liver failure: Interleukin-22.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Review
  20. Review
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

11 authors at 7 institutions in 3 countries.

Dechun FengLaboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892;
Yan WangLaboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892;
Hua WangLaboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892;
Honglei WengMedical Clinic, Faculty of Medicine at Mannheim, University of Heidelberg, Mannheim 68167, Germany;
Xiaoni KongSchool of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China; Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China; and.
Brittany V Martin-MurphySkaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045.
Yongmei LiLaboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892;
Ogyi ParkLaboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892;
Steven DooleyMedical Clinic, Faculty of Medicine at Mannheim, University of Heidelberg, Mannheim 68167, Germany;
Cynthia JuSkaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045.
Bin GaoLaboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892; bgao@mail.nih.gov.
National Institutes of Health · USHeidelberg University · DENational Institute on Alcohol Abuse and Alcoholism · USShanghai Jiao Tong University · CNUniversity Medical Centre Mannheim · DEUniversity of Colorado Anschutz Medical Campus · USUniversity of Montana · US

Funding

Pathogenesis and Novel Therapeutic Targets of Steatotic Liver Disease and CancerZIAAA000369 · NIAAA · NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM · PI GAO, BIN · 2009 to 2025
$23.4M
Molecular mechanisms of liver injury, repair, and immunityZIAAA000368 · NIAAA · NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM · PI GAO, BIN · 2009 to 2023
$16.1M
Intramural NIH HHS Z99 AA999999Intramural NIH HHS ZIA AA000369
6 · The paper itself

Abstract

Acetaminophen (APAP)-induced liver injury (AILI) accounts for half of the acute liver failure cases in the United States. A better understanding of the underlying mechanisms of AILI is necessary for the development of novel antidotes. We found that pretreatment with IL-22 protected mice from APAP-mediated hepatotoxicity. The protection was dependent on STAT3, as IL-22 failed to reduce APAP hepatotoxicity in liver-specific STAT3 knockout mice. In contrast to the acute exposure to IL-22, the endogenous chronic overexpression of IL-22 in IL-22 transgenic (TG) mice or IL-22 adenovirus treatment for 6 wk resulted in a markedly increased susceptibility to AILI. Furthermore, the hepatic expression levels of cytochrome 2E1 (Cyp2E1) and Cyp1A2 were much higher in IL-22TG mice. Ablation of Cyp2E1 but not hepatic STAT3 abolished AILI and protein-adduct formation in IL-22TG mice. Finally, hepatic expression of HNF-1α, a transcriptional factor that is known to control Cyp2E1 expression, was elevated in IL-22TG mice compared with wild-type mice. Upregulation of hepatic Cyp2E1 was only observed in mice with constitutive overexpression of IL-22 but not with short-term treatment with one dose of IL-22 or multiple doses of IL-22 for 2 wk. In conclusion, short-term acute IL-22 exposure protects mice against AILI through STAT3 activation; however, chronic constitutive overexpression of IL-22 exacerbates AILI by increasing Cyp2E1 and toxic reactive APAP metabolite production. These findings may not only enhance our understanding of the effects of chronic inflammation on AILI in patients with liver disease, but are also helpful to identify novel therapeutic targets for the treatment of AILI.

Indexed as

AcetaminophenAcute DiseaseAnalgesics, Non-NarcoticAnimalsChemical and Drug Induced Liver InjuryChronic DiseaseCytochrome P-450 CYP2E1Gene Expression Regulation, EnzymologicHepatocyte Nuclear Factor 1-alphaHumansInterleukin-22InterleukinsMiceMice, KnockoutSTAT3 Transcription FactorAcetaminophenAnalgesics, Non-NarcoticCytochrome P-450 CYP2E1Hepatocyte Nuclear Factor 1-alphaHnf1a protein, mouseInterleukin-22InterleukinsStat3 protein, mouseSTAT3 Transcription Factor

Identifiers

PMID25063867
PMCPMC4135042
OpenAlexW2154762892

What OpenQuestion holds

Textmetadata
LicenceTDM
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.