Research Papers:

Down-regulation of toll-like receptor 4 alleviates intestinal ischemia reperfusion injury and acute lung injury in mice

Qiankun Zhu, Guizhen He _, Jie Wang, Yukang Wang, Wei Chen and Tai Guo

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Oncotarget. 2017; 8:13678-13689. https://doi.org/10.18632/oncotarget.14624

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Qiankun Zhu1, Guizhen He1, Jie Wang1, Yukang Wang1, Wei Chen1, Tai Guo2

1Department of Parenteral and Enteral Nutrition, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China

2National Institute for the Control of Pharmaceutical and Biological Products, China

Correspondence to:

Guizhen He, email: [email protected]

Keywords: toll-like receptor 4 (TLR4), intestinal ischemia reperfusion (IR), acute lung injury (ALI), inflammatory response, oxidative stress

Received: July 11, 2016     Accepted: January 06, 2017     Published: January 13, 2017


Intestinal ischemia reperfusion (IR) injury is a critical problem, which can cause intestinal injury locally and acute lung injury (ALI) distally by inflammatory responses and oxidative stress. Toll-like receptor 4 (TLR4) is involved in innate immune and inflammatory responses. This study was to determine whether TLR4 mutant can attenuate intestinal and lung injuries after intestinal IR. Wild type (WT) and TLR4 mutant mice were submitted to intestinal IR by occluding the superior mesenteric artery. Histological assessment of the intestine and the lung were conducted by HE staining. The levels of proinflammatory cytokines, oxidative stress markers, apoptotic index and other mediators were measured. In addition, a 24-hour survival study was performed. Histological assessment showed that intestinal IR caused serious injuries in the intestine and the lung, corroborated by increased proinflammatory cytokines in the circulation. TLR4 mutant suppressed the histological injuries as demonstrated by significantly decreased pathological scores. Consistent with the morphological results, the TLR4 mutant mice exhibited remarkably lowered cytokine expressions in the intestine (TNF-α, IL-6, IL-1β, and NF-κB) and the lung (NO, iNOS, MCP-1, MIP-2, NF-κB, and Caspase-3). ALT and creatinine were also significantly dampened in the liver and kidney, respectively. Furthermore, the survival rate over the course of 24 hours was significantly improved. Collectively, the findings reveal that TLR4 mutant significantly abated the intestinal IR injury and ALI at least in part by alleviating the inflammatory response and oxidative stress.

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