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Inhibition of Bcl2L12 Attenuates Eosinophilia-Related Inflammation in the Heart

Authors
  • Chen, Xiao1
  • Zhao, Mei-Zhen2
  • Miao, Bei-Ping3
  • Liu, Zhi-Qiang2
  • Yang, Gui4
  • Liu, Jiang-Qi2
  • Yang, Ping-Chang2, 5
  • Song, Jiang-Ping1
  • 1 State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing , (China)
  • 2 Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen , (China)
  • 3 Department of Otolaryngology, First Affiliated Hospital of Shenzhen University, Shenzhen , (China)
  • 4 Department of Otolaryngology, Longgang Central Hospital, Shenzhen , (China)
  • 5 Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen , (China)
Type
Published Article
Journal
Frontiers in Immunology
Publisher
Frontiers Media SA
Publication Date
Sep 11, 2020
Volume
11
Identifiers
DOI: 10.3389/fimmu.2020.01955
PMID: 33013849
PMCID: PMC7516035
Source
PubMed Central
Keywords
License
Unknown

Abstract

Background: The eosinophilic inflammation plays a critical role in myocarditis (Mcd); its underlying mechanism remains to be further elucidated. This study aims to investigate the role of Bcl2-like protein 12 (Bcl2L12) in inducing the defects of apoptosis in eosinophils (Eos) of the heart tissues. Methods: Human explant heart samples were collected. Eosinophilia and myocarditis (Mcd)-like inflammation were induced in the mouse heart by immunizing with murine cardiac α-myosin heavy chain (MyHCα) peptides. Results: Markedly more Eos were observed in heart tissues from patients with Mcd than those from patients with dilated cardiomyopathy. Eos isolated from Mcd hearts showed the signs of apoptosis defects. The Eo counts in the Mcd heart tissues were positively correlated with the Bcl2L12 expression in Eos isolated from the heart tissues. Exposure to interleukin 5 in the culture induced the expression of Bcl2L12 in Eos. Bcl2L12 bound c-Myc, the transcription factor of Fas ligand (FasL), to prevent c-Myc from binding to the FasL promoter, to restrict the FasL gene transcription in Eos. Inhibition of Bcl2L12 prevented the induction of eosinophilia and Mcd-like inflammation in the mouse heart. Conclusions: The Bcl2L12 expression contributes to apoptosis defects in Eos of the Mcd heart. Blocking Bcl2L12 prevents the eosinophilia induction and alleviates Mcd-like inflammation in mice.

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