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Cited by 48Atherosclerosis and Cardiovascular DiseasesCholesterol and Lipid MetabolismCardiac Fibrosis and Remodeling

Deficiency of programmed cell death 4 results in increased IL-10 expression by macrophages and thereby attenuates atherosclerosis in hyperlipidemic mice

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Jiang, Yang, Gao, Qi, Wang, Liyang, Guo, Chun, Zhu, Faliang, Wang, Bo, Wang, Qun, Gao, Fei +2 more·2016·Cellular & Molecular Immunology
DOI 10.1038/cmi.2015.47PMC PMC4947820
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Abstract

Programmed cell death 4 (Pdcd4) is a newly defined inhibitor of transcription and translation and a tumor suppressor. Recent studies have suggested that Pdcd4 may also be involved in some inflammatory diseases. However, its role in atherosclerosis, a chronic inflammation of the arterial wall, remains to be investigated. Here, we found that Pdcd4 deficiency in mice increased the expression of IL-10 in macrophages and decreased the expression of IL-17 in T cells in the presence of an atherosclerosis-associated stimulator in vitro and in high fat-induced atherosclerotic plaques. Importantly, knocking out Pdcd4 led to a decrease in atherosclerotic lesions in Apoe(-/-) mice fed a high fat diet. This effect could be partly reversed by blocking IL-10 with a neutralizing antibody but not by the application of exogenous IL-17. Further mechanistic studies revealed that Pdcd4 negatively regulated the expression of IL-10 in an ERK1/2- and p38-dependent manner. These results demonstrate that Pdcd4 deficiency attenuates atherosclerosis in hyperlipidemic mice in part through the upregulation of the anti-inflammatory cytokine IL-10. This indicates that endogenous Pdcd4 promotes atherosclerosis and therefore represents a potential therapeutic target for patients with atherosclerosis.

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Cited by

Sorted by citations

Authors
Jiang, Y., Gao, Q., Wang, L., Guo, C., Zhu, F., Wang, B., Wang, Q., Gao, F., Chen, Y., & Zhang, L.
Affiliations
  • Shandong University (CN)
  • University of Pennsylvania (US)
ORCID
Venue
Cellular & Molecular Immunology
Publisher
Springer Science and Business Media LLC
Published
2015-07-13
Volume
13
Issue
4
Pages
524-534
ISSN
  • 1672-7681 (ISSN-L)
  • 2042-0226
DOI
10.1038/cmi.2015.47
PMC
PMC4947820
OpenAlex
W2144960153
Cited by
48
References
4
Citations by year
2026: 4 · 2025: 2 · 2024: 3 · 2023: 9 · 2022: 3 · 2021: 7 · 2020: 4 · 2019: 2 · 2018: 3 · 2017: 4 · 2016: 7
FWCI
2.30
Type
journal article
Language
en
Open access
Licence
Locations
  • Cellular and Molecular Immunology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
Keywords
PDCD4, IL-10, macrophages, atherosclerosis, hyperlipidemia, IL-17, ERK signaling, p38 MAPK, anti-inflammatory cytokines, ApoE-deficient mice, high-fat diet, chronic inflammation, atherosclerotic plaque
MeSH terms
Animals, Apolipoproteins E, Female, Hyperlipidemias, Lipoproteins, LDL, Male, Mice, Inbred C57BL, Recombinant Proteins, T-Lymphocytes, RNA-Binding Proteins, Interleukin-10, Macrophages, Peritoneal, Interleukin-17, MAP Kinase Signaling System, Atherosclerosis, Apoptosis Regulatory Proteins, Antibodies, Neutralizing, Plaque, Atherosclerotic

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