FGL2 敲低通过调节实验性自身免疫性心肌炎大鼠 TLR9 信号改善心脏功能。

FGL2 knockdown improves heart function through regulation of TLR9 signaling in the experimental autoimmune myocarditis rats.

机构信息

Department of Cardiology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, People's Republic of China.

Vascular Biology Program, Boston Children's Hospital, Department of Surgery, Harvard Medical School, Boston, MA, 02115, USA.

出版信息

Immunol Res. 2018 Feb;66(1):52-58. doi: 10.1007/s12026-017-8965-4.

DOI:10.1007/s12026-017-8965-4

PMID:29128901

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11025570/

Abstract

Fibrinogen-like protein 2 (FGL2) is an important immune regulator of both innate and adaptive response. It is present on the surface of macrophages and endothelial cells, and can be constitutively secreted by CD4CD8 T cells. Previous studies showed that FGL2 is a potential target for the treatment of experimental autoimmune myocarditis. However, the molecular mechanism of the roles of FGL2 in experimental autoimmune myocarditis is poorly understood. Here, we silenced FGL2 gene by using FGL2-RNAi lentivirus to reveal the heart function in experimental autoimmune myocarditis rats. We found that the cardiac myosin of pigs' hearts induced Lewis rats to come into being as autoimmune myocarditis. TLR9 was upregulated in the heart of experimental autoimmune myocarditis rats. After primary immunization (21 day), the cardiac function of the myocarditis model group improved (P < 0.05). Significantly, the levels of INF-α and NF-κB in the FGL2-RNAi-treated group were lower compared to those in the myocarditis model (EAM) group (P < 0.05). Notably, the inflammation score correspondence with the protein and mRNA levels of TLR9 in myocardial tissues was markedly reduced compared to that in the EAM group (P < 0.05). These results support a role of FGL2 to alleviate inflammatory situation in the myocardium through regulation of the TLR9 signaling pathway in the experimental autoimmune myocarditis rats.

摘要

纤维蛋白原样蛋白 2（FGL2）是先天和适应性免疫反应的重要免疫调节剂。它存在于巨噬细胞和内皮细胞表面，并且可以由 CD4CD8 T 细胞持续分泌。先前的研究表明，FGL2 是治疗实验性自身免疫性心肌炎的潜在靶标。然而，FGL2 在实验性自身免疫性心肌炎中的作用的分子机制尚不清楚。在这里，我们使用 FGL2-RNAi 慢病毒沉默 FGL2 基因，以揭示实验性自身免疫性心肌炎大鼠的心脏功能。我们发现猪心脏肌球蛋白诱导 Lewis 大鼠产生自身免疫性心肌炎。TLR9 在实验性自身免疫性心肌炎大鼠的心脏中上调。在初次免疫（21 天）后，心肌炎模型组的心脏功能得到改善（P<0.05）。值得注意的是，与心肌炎模型（EAM）组相比，FGL2-RNAi 处理组的 INF-α 和 NF-κB 水平较低（P<0.05）。值得注意的是，与 EAM 组相比，心肌组织中 TLR9 的蛋白和 mRNA 水平的炎症评分明显降低（P<0.05）。这些结果支持 FGL2 通过调节实验性自身免疫性心肌炎大鼠 TLR9 信号通路来减轻心肌炎症情况的作用。