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27 August 2018 : Animal Research  

Activation of the Nuclear Erythroid 2-Related Factor 2 Antioxidant Responsive Element (Nrf2-ARE) Signaling Pathway Alleviates Acute Graft-Versus-Host Disease by Reducing Oxidative Stress and Inhibiting Infiltration of Inflammatory Cells in an Allogeneic Stem Cell Transplantation Mouse Model

Ting Yi12BCD, Xiaogang Li3BF, Erhua Wang1B, Yanan Zhang1D, Yunfeng Fu1C, Jieping Li2A, Tiebin Jiang1AG*

DOI: 10.12659/MSM.908130

Med Sci Monit 2018; 24: ANS5973-5979

Abstract

BACKGROUND: Acute graft-versus-host disease (aGVHD) limits the wider application of hematopoietic stem cell transplantation (HSCT). We explored the relationship between the Nrf2-ARE signaling pathway and aGVHD and identified effective and efficient therapeutic targets for the prevention and management of aGVHD following HSCT.

MATERIAL AND METHODS: C57BL/6 and BALB/c mice were used to establish the aGVHD model. The bone marrow and spleen mononuclear cells were separated from the donor mice and injected into the caudal vein of recipient mice that had undergone total body irradiation (TBI, 8 Gy). Sulforaphane (SFN) was used to activate the Nrf2-ARE signaling pathway.

RESULTS: The long-term survival rate of the SFN group was higher than that of the control group (40% vs. 0%, p<0.05, n=10). There were worse pathological changes and a greater infiltration of inflammatory cells in the liver, small intestine, and lung tissues of the control group. Furthermore, the Nrf2, NQO1, and HO-1 mRNA and protein levels were higher in the small intestines of the SFN group than in the control group (p<0.05, n=4).

CONCLUSIONS: The Nrf2-ARE signaling pathway plays a vital role in preventing aGVHD in an HSCT mouse model by regulating the expression of the downstream antioxidant genes NQO1 and HO-1 and by inhibiting the local inflammatory reaction.

Keywords: Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, NF-E2-Related Factor 1

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750