Evidence map›Paper›PMID 36928191›Full record

ArticleJCI insight2023

Impaired PPARγ activation by cadmium exacerbates infection-induced lung injury.

Jennifer L Larson-Casey, Shanrun Liu, Jennifer M Pyles, Suzanne E Lapi, Komal Saleem, Veena B Antony, Manuel Lora Gonzalez, David K Crossman, A Brent Carter

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.7field-weighted citation impact, top 11% 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

9 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Dietary influence on lung injury and immune modulation in cadmium-exposed mice.American journal of physiology. Lung cellular and molecular physiology · 2025
    Article
  5. Article
  6. Article
  7. Observational
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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

9 authors at 1 institution in 1 country.

Jennifer L Larson-CaseyDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine.
Shanrun LiuDivision of Clinical Immunology and Rheumatology, Department of Medicine.
Jennifer M PylesDepartment of Radiology.
Suzanne E LapiDepartment of Radiology.
Komal SaleemDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine.
Veena B AntonyDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine.
Manuel Lora GonzalezDepartment of Pathology, and.
David K CrossmanDepartment of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
A Brent CarterDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine.
University of Alabama at Birmingham · US

Funding

XRAY CRYSTALLOGRAPHYP30CA013148 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Robert S Welner · 1985 to 2026
$165.9M
Virology CoreP30AI027767 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Latesha Ellen Elopre · 1988 to 2026
$84.1M
Therapeutic Targeting of the Myofibroblast in Fibrotic Lung DiseaseP01HL114470 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI THANNICKAL, VICTOR J. · 2013 to 2022
$17.8M
Project 5 Nano-micro Hybrid Fibrous Materials for Containment Removal and Site RemediationP42ES027723 · NIEHS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI ANTONY, VEENA B. · 2020 to 2024
$6.7M
Lung Macrophage Metabolic Reprogramming in Asbestos-Induced ToxicityR01ES015981 · NIEHS · UNIVERSITY OF IOWA · PI CARTER, A BRENT · 2007 to 2022
$5.5M
Environmental Cadmium and COPDR01ES029981 · NIEHS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI ANTONY, VEENA B. · 2018 to 2022
$2.5M
CSRD VA I01 CX001715NCI NIH HHS P30 CA013148NHLBI NIH HHS P01 HL114470NIAID NIH HHS P30 AI027767NIEHS NIH HHS P42 ES027723NIEHS NIH HHS R01 ES015981NIEHS NIH HHS R01 ES029981
6 · The paper itself

Abstract

Emerging data indicate an association between environmental heavy metal exposure and lung disease, including lower respiratory tract infections (LRTIs). Here, we show by single-cell RNA sequencing an increase in Pparg gene expression in lung macrophages from mice exposed to cadmium and/or infected with Streptococcus pneumoniae. However, the heavy metal cadmium or infection mediated an inhibitory posttranslational modification of peroxisome proliferator-activated receptor γ (PPARγ) to exacerbate LRTIs. Cadmium and infection increased ERK activation to regulate PPARγ degradation in monocyte-derived macrophages. Mice harboring a conditional deletion of Pparg in monocyte-derived macrophages had more severe S. pneumoniae infection after cadmium exposure, showed greater lung injury, and had increased mortality. Inhibition of ERK activation with BVD-523 protected mice from lung injury after cadmium exposure or infection. Moreover, individuals residing in areas of high air cadmium levels had increased cadmium concentration in their bronchoalveolar lavage (BAL) fluid, increased barrier dysfunction, and showed PPARγ inhibition that was mediated, at least in part, by ERK activation in isolated BAL cells. These observations suggest that impaired activation of PPARγ in monocyte-derived macrophages exacerbates lung injury and the severity of LRTIs.

Indexed as

Lung InjuryPPAR gammaAnimalsCadmiumLungMacrophages, AlveolarMiceCadmiumPPAR gammaBacterial infectionsInfectious diseaseInnate immunityMacrophagesPulmonology

Identifiers

PMID36928191
PMCPMC10243824
OpenAlexW4327574196

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.