Oncotarget

Research Papers: Immunology:

Nrf2 plays a pivotal role in protection against burn trauma-induced intestinal injury and death

Zhao Chen, Yiran Zhang, Liang Ma, Yiming Ni and Haige Zhao _

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Oncotarget. 2016; 7:19272-19283. https://doi.org/10.18632/oncotarget.8189

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Abstract

Zhao Chen1,*, Yiran Zhang1,*, Liang Ma1, Yiming Ni1 and Haige Zhao1

1 Department of Cardiothoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

* These authors have contributed equally to this study

Correspondence to:

Haige Zhao, email:

Keywords: Nrf2, burn trauma, intestinal injury, systemic inflammation, Immunology and Microbiology Section, Immune response, Immunity

Received: January 09, 2016 Accepted: March 05, 2016 Published: March 18, 2016

Abstract

Nuclear factor (erythroid-derived 2)–like 2 (NRF2) is a basic leucine zipper transcription factor that principally defends against oxidative stress and also plays a unique role in severe sepsis. However, its contribution to intestinal injury and death after burn trauma is unclear.In this study, wild-type (Nrf2+/+) and Nrf2-deficient (Nrf2−/−) mice were subjected to 15% or 30% total body surface area burn or sham injury. Survival, systemic inflammation, and gut injury were determined.Nrf2−/− mice were more susceptible to burn-induced intestinal injury, as characterized by increases in damage to the gut structure and in intestinal permeability. This exacerbation was associated with an increase in the intestinal mRNA expression of inflammatory cytokines (interleukin [IL]–6, IL-1B, monocyte chemotactic protein 1, intercellular adhesion molecule, and vascular cell adhesion molecule) and a decrease in the intestinal mRNA expression of Nrf2-regulated genes (NAD(P)H dehydrogenasequinine-1 and glutamate-cysteine ligase modifier subunit). Nrf2-deficient mice also showed a lower survival rate and higher levels of systemic cytokines (IL-6 and IL-1B) and high-mobility group protein B1 than wild-type mice. This study demonstrates for the first time that mice that lack Nrf2 are more susceptible to burn-induced intestinal injury and have more systemic inflammation and a lower survival rate.


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