Open AccessSoluble fibrinogen‐like protein 2 ameliorates acute rejection of liver transplantation in rat via inducing Kupffer cells M2 polarization
Author(s) -
Pan Guangrui,
Zhao Zhengfei,
Tang Chengyong,
Ding Liuyue,
Li Zhongtang,
Zheng Daofeng,
Zong Liang,
Wu Zhongjun
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1528
Subject(s) - in vivo , transplantation , liver transplantation , secretion , medicine , fibrinogen , in vitro , tumor necrosis factor alpha , downregulation and upregulation , chemistry , biology , biochemistry , gene , microbiology and biotechnology
Soluble fibrinogen‐like protein 2 ( sFGL 2) could ameliorate acute rejection ( AR ) in rat cardiac transplantation. However, the role of sFGL 2 in AR of liver transplantation has not been addressed. In this study, we found that FGL 2 was upregulated in rat orthotropic liver transplantation ( OLT ) models of tolerance and positive correlation with the frequency of M2 Kupffer cells ( KC s). Gain‐of‐function experiments in vitro showed that sFGL 2 promoted the secretion of anti‐inflammatory cytokines ( IL ‐10, TGF ‐β) and the expression of CD 206, and inhibited the activities of STAT 1 and NF ‐κB signaling pathway. Consistently, in vivo assays showed that adeno‐associated virus‐mediated FGL 2 ( AAV ‐ FGL 2) transfer to recipients could ameliorate AR of rat OLT and induce KC s M2 polarization in allografts. Notably, we found that the recipients receiving transferred KC s from AAV ‐ FGL 2‐treated allograft showed alleviated AR . Taken together, we revealed that sFGL 2 ameliorated AR by inducing KC s M2 polarization.