Fibrinogen‐like protein‐2 causes deterioration in cardiac function in experimental autoimmune myocarditis rats through regulation of programmed death‐1 and inflammatory cytokines. Issue 2 (16th October 2017)

• Record Type: Journal Article
• Authors: Zheng, Zhenzhong; Yu, Yinghui; Potla, Ratnakar; Wu, Yujing; Wu, Hao
• Is Part Of: Immunology. Volume 153:Issue 2(2018)
• Page Start: 246
• Page End: 252
• Publication Date: 2017-10-16
• Subjects: cardiac function -- experimental autoimmune myocarditis -- fibrinogen‐like protein‐2 -- inflammatory cytokines -- programmed death‐1; Immunology -- Periodicals
• DOI: 10.1111/imm.12837
• Languages: English
• ISSNs: 0019-2805

Abstract

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 (FGL2) 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 FGL2. Over‐expression of FGL2 significantly decreased PD‐1 and deteriorated cardiac function in rats with autoimmune myocarditis. Histopathology revealed increased inflammatory cell infiltrate in EAM‐FGL2 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 FGL2 over‐expressing EAM rats. Hence, FGL2 plays an important role in the pathogenesis of autoimmune myocarditis that also involves the PD‐1/PD‐L1 pathway. Our findings may provide novel therapeutic targets for the treatment of immune‐induced heart injury. Abstract : In our current study, we showed that fibrinogen‐like protein‐2 (FGL2) caused a deterioration in cardiac function by increasing inflammatory cell infiltration and elevating the serum levels of brain natriuretic peptide, interleukin‐6, interleukin‐17 and interferon‐ γ . FGL2 over‐expression down‐regulated programmed death‐1 and up‐regulated retinoic acid‐related orphan receptor γ t and transcription factor forkhead box P3 levels in rats with autoimmune myocarditis.