Evidence map›Paper›PMID 33839155›Full record

ArticleThe Journal of biological chemistry

Interferon regulatory factor 8 regulates expression of acid ceramidase and infection susceptibility in cystic fibrosis.

Aaron Ions Gardner, Yuqing Wu, Rabea Verhaegh, Yongjie Liu, Barbara Wilker, Matthias Soddemann, Simone Keitsch, Michael J Edwards, Iram J Haq, Markus Kamler and 3 more

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

Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.6field-weighted citation impact, top 32% 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

5 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Unleashing AdipoRon's Potential: A Fresh Approach to TackleJournal of inflammation research · 2024
    Article
  5. Article
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

13 authors at 5 institutions in 3 countries.

Aaron Ions GardnerFaculty of Medical Sciences, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
Yuqing WuDepartment of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Rabea VerhaeghDepartment of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Yongjie LiuDepartment of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; Department of Thoracic and Cardiovascular Surgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Barbara WilkerDepartment of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Matthias SoddemannDepartment of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Simone KeitschDepartment of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Michael J EdwardsDepartment of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Iram J HaqFaculty of Medical Sciences, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK; Pediatric Respiratory Medicine, Great North Children's Hospital, Newcastle upon Tyne, UK.
Markus KamlerDepartment of Thoracic and Cardiovascular Surgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Katrin Anne BeckerDepartment of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Malcolm BrodlieFaculty of Medical Sciences, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK; Pediatric Respiratory Medicine, Great North Children's Hospital, Newcastle upon Tyne, UK. Electronic address: malcolm.brodlie@ncl.ac.uk.
Erich GulbinsDepartment of Thoracic and Cardiovascular Surgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. Electronic address: erich.gulbins@uni-due.de.
University of Duisburg-Essen · DEEssen University Hospital · DEGreat North Children's Hospital · GBNewcastle University · GBUniversity of Cincinnati Medical Center · US

Funding

Medical Research Council MC_PC_16054Medical Research Council MR/M008797/1
6 · The paper itself

Abstract

Most patients with cystic fibrosis (CF) suffer from acute and chronic pulmonary infections with bacterial pathogens, which often determine their life quality and expectancy. Previous studies have demonstrated a downregulation of the acid ceramidase in CF epithelial cells resulting in an increase of ceramide and a decrease of sphingosine. Sphingosine kills many bacterial pathogens, and the downregulation of sphingosine seems to determine the infection susceptibility of cystic fibrosis mice and patients. It is presently unknown how deficiency of the cystic fibrosis transmembrane conductance regulator (CFTR) connects to a marked downregulation of the acid ceramidase in human and murine CF epithelial cells. Here, we employed quantitative PCR, western blot analysis, and enzyme activity measurements to study the role of IRF8 for acid ceramidase regulation. We report that genetic deficiency or functional inhibition of CFTR/Cftr results in an upregulation of interferon regulatory factor 8 (IRF8) and a concomitant downregulation of acid ceramidase expression with CF and an increase of ceramide and a reduction of sphingosine levels in tracheal and bronchial epithelial cells from both human individuals or mice. CRISPR/Cas9- or siRNA-mediated downregulation of IRF8 prevented changes of acid ceramidase, ceramide, and sphingosine in CF epithelial cells and restored resistance to Pseudomonas aeruginosa infections, which is one of the most important and common pathogens in lung infection of patients with CF. These studies indicate that CFTR deficiency causes a downregulation of acid ceramidase via upregulation of IRF8, which is a central pathway to control infection susceptibility of CF cells.

Indexed as

Acid CeramidaseAnimalsCeramidesCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorEpithelial CellsHumansInterferon Regulatory Factor-8Interferon Regulatory FactorsLungMiceMice, KnockoutPseudomonas aeruginosaPseudomonas InfectionsSphingosineAcid CeramidaseCeramidesCFTR protein, humanCystic Fibrosis Transmembrane Conductance RegulatorInterferon Regulatory Factor-8Interferon Regulatory FactorsSphingosineacid ceramidaseceramidecystic fibrosisinterferon response factor-8Pseudomonas aeruginosasphingosine

Identifiers

PMID33839155
PMCPMC8113888
OpenAlexW3155048251

What OpenQuestion holds

Textmetadata
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.