Premium
Fibrinogen‐like protein‐2 causes deterioration in cardiac function in experimental autoimmune myocarditis rats through regulation of programmed death‐1 and inflammatory cytokines
Author(s) -
Zheng Zhenzhong,
Yu Yinghui,
Potla Ratnakar,
Wu Yujing,
Wu Hao
Publication year - 2018
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12837
Subject(s) - myocarditis , foxp3 , medicine , inflammation , immune system , cardiac function curve , interleukin , immunology , endocrinology , pathogenesis , cytokine , heart failure
Summary Programmed death‐1 ( PD ‐1) plays an important role in protecting against inflammation and myocyte damage in T‐cell‐mediated myocarditis. To understand whether fibrinogen‐like protein‐2 ( FGL 2) can affect the role of the PD ‐1/ PD ‐L1 pathway in experimental autoimmune myocarditis ( EAM ), we investigated cardiac function in EAM rats over‐expressing FGL 2. Over‐expression of FGL 2 significantly decreased PD ‐1 and deteriorated cardiac function in rats with autoimmune myocarditis. Histopathology revealed increased inflammatory cell infiltrate in EAM ‐ FGL 2 rats compared with the control groups ( EAM , EAM ‐ GFP and NC ). Notably, transcription factor forkhead box P3 (Foxp3) and retinoic acid‐related orphan receptor γ t ( ROR γ t) protein and mRNA levels were statistically ( P < 0·05) increased in EAM rats. We also found that interferon‐ γ , interleukin‐6, interleukin‐17 and brain natriuretic peptide levels were profoundly increased in serum of FGL 2 over‐expressing EAM rats. Hence, FGL 2 plays an important role in the pathogenesis of autoimmune myocarditis that also involves the PD ‐1/ PD‐L 1 pathway. Our findings may provide novel therapeutic targets for the treatment of immune‐induced heart injury.