Evidence map›Paper›PMID 39895606›Full record

ArticleAllergy, asthma & immunology research2025

Peroxisome Metabolism Pathway and EHHADH Expression are Downregulated in Macrophages in Neutrophilic Asthma.

Gongqi Chen, Wei Gu, Chunli Huang, Weiqiang Kong, Lu Zhao, Huiru Jie, Guohua Zhen

Abstract read
In one paragraph

Article in Allergy, asthma & immunology research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

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0cells of the map it votes in
4citing papers in PubMed
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1 · What the graph read from it

What it found

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3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Gongqi ChenDivision of Respiratory and Critical Care Medicine, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.ORCID https://orcid.org/0009-0009-4860-1335
Wei GuDivision of Respiratory and Critical Care Medicine, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Chunli HuangDivision of Respiratory and Critical Care Medicine, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Weiqiang KongDivision of Respiratory and Critical Care Medicine, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Lu ZhaoDivision of Respiratory and Critical Care Medicine, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Huiru JieDivision of Respiratory and Critical Care Medicine, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Guohua ZhenDivision of Respiratory and Critical Care Medicine, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.ORCID https://orcid.org/0000-0001-5582-7900

Funding

Key Research and Development Program of Hubei Province 2024BCB042National Natural Science Foundation of China 82170036Tongji Hospital 2023CXZH006
6 · The paper itself

Abstract

purposeNeutrophilic asthma (NA) is associated with more severe symptoms and poor responsiveness to inhaled corticosteroid therapy. Macrophages are the most abundant immune cells in the airway, but the role of macrophages in NA pathogenesis has not been fully studied. We hypothesized that dysregulation of peroxisome metabolism in macrophages may drive NA.

methodsWe retrieved microarray datasets from the GEO Gene Expression Omnibus database by using induced sputum samples from eosinophilic and neutrophilic asthma patients as well as healthy controls. We identified key molecules in NA and validated the expression of the key genes in our cohort of asthma patients using quantitative polymerase chain reaction (PCR). Furthermore, immunofluorescence staining was performed to detect the expression and localization of the key molecule in bronchoalveolar lavage (BAL) cells from asthma patients and the murine model of neutrophilia-dominant allergic airway inflammation. The expression of the key molecule was also examined in mouse bone marrow-derived macrophages (BMDMs) by quantitative PCR and western blotting.

resultsEnoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (EHHADH), sterol carrier protein 2, and peroxisomal biogenesis factor 14 were identified as the key molecules and were downregulated in patients with NA or severe asthma. The peroxisomal fatty acid metabolism pathway was significantly downregulated in NA. In our cohort of asthma patients, the expression of EHHADH, a key enzyme of the peroxisomal fatty acid beta-oxidation, was significantly decreased in non-eosinophilic asthma patients and positively correlated with airflow limitation. EHHADH was primarily expressed in macrophages in BAL cells. EHHADH was downregulated in lipopolysaccharide (LPS)-induced M1-like macrophages in mouse BMDMs. Fenofibrate, an agonist of the peroxisome pathway, significantly inhibits LPS-induced macrophage M1 polarization.

conclusionsEHHADH expression and the peroxisome metabolism pathway are downregulated in macrophages in patients with NA. This downregulation may contribute to macrophage M1 polarization and neutrophilic airway inflammation in asthma.

Indexed as

AsthmaEHHADH proteinmacrophagesneutrophilsperoxisomesPEX14 proteinsterol carrier protein 2

Identifiers

PMID39895606
PMCPMC11791367

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