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.
Highlights
It is estimated that about 400,000 persons die of heart inflammatory diseases each year in the world [1]
Eos were isolated from Mcd and dilated cardiomyopathy (Dcm) heart samples and healthy subject blood samples
Fas expression was detected in both Mcd Eos and Dcm Eos without significant difference (Figures 2K,L), whereas Fas ligand (FasL) expression was lower in Mcd Eos than that in Dcm Eos (Figures 2M,N)
Summary
It is estimated that about 400,000 persons die of heart inflammatory diseases each year in the world [1]. Eosinophilia is a pathological sign in many inflammatory disorders. It indicates that the eosinophil (Eo) number is unusually increased in the local tissues, which may be reflected by the Eo frequency in peripheral white blood cells. Eosinophilia commonly occurs in allergic disorders, parasite infection, neoplasia, or autoimmune diseases [3], as well as in myocarditis (Mcd) [4]. 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
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