IL-4 Alleviates Ischaemia-Reperfusion Injury by Inducing Kupffer Cells M2 Polarization via STAT6-JMJD3 Pathway after Rat Liver Transplantation

  • Biomed Res Int. 2020 Mar 18;2020:2953068. doi: 10.1155/2020/2953068.
Minghua Deng  1 ,  Jingyuan Wang  1 ,  Hao Wu  1 ,  Menghao Wang  1 ,  Ding Cao  1 ,  Jinzheng Li  1 ,  Yakun Wu  2 ,  Jianping Gong  1
Affiliations
  • 1. Department of Hepatobiliary Surgery, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
  • 2. Department of Hepatobiliary Surgery, Suining Central Hospital, Suining, Sichuan 629000, China.
PMID: 32258110 DOI: 10.1155/2020/2953068
Abstract

Background: Liver ischaemia-reperfusion injury (IRI) remains a problem in liver transplantation. Interleukin-4 (IL-4) has been found to reduce liver IRI, but the exact mechanism remains unclear.

Methods: Donor livers were infused with recombinant IL-4 or normal saline during cold storage, and the hepatocellular Apoptosis and the inflammatory response were detected. The effect of IL-4 treatment on Kupffer cells (KCs) polarization and expression of the STAT6-JMJD3 pathway was evaluated in vivo and in vitro. KCs in donor livers were depleted by clodronate Liposome treatment or JMJD3 was inhibited by GSK-J4 before liver transplantation to determine whether the protective effect of IL-4 treatment was dependent on KCs.

Results: IL-4 treatment decreased sALT and sAST levels and alleviated hepatocellular Apoptosis and inflammation at 6 h after liver transplantation. IL-4 treatment induced KCs alternatively activated (M2) polarization in vitro. KCs in donor livers were depleted by clodronate Liposome treatment or JMJD3 was inhibited by GSK-J4 before liver transplantation to determine whether the protective effect of IL-4 treatment was dependent on KCs. in vivo and in vitro. KCs in donor livers were depleted by clodronate Liposome treatment or JMJD3 was inhibited by GSK-J4 before liver transplantation to determine whether the protective effect of IL-4 treatment was dependent on KCs.

Conclusions: IL-4 treatment-induced KCs M2 polarization was dependent on the STAT6-JMJD3 pathway and protected liver grafts from IRI after liver transplantation.

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