Oncotarget

Research Papers: Pathology:

Ilomastat, a synthetic inhibitor of MMPs, prevents lung injury induced by γ-ray irradiation in mice

Xiaoman Li, Dehui Ma, Xiaodan Zha, Dongqin Quan, Dong Pan, Manji Sun, Burong Hu and Baoquan Zhao _

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Oncotarget. 2017; 8:60789-60808. https://doi.org/10.18632/oncotarget.18487

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Abstract

Xiaoman Li1,2,3,5, Dehui Ma4, Xiaodan Zha4, Dongqin Quan1, Dong Pan2,3,5, Manji Sun1, Burong Hu2,3 and Baoquan Zhao1

1 State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China

2 CAS Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China

3 Key Laboratory of Space Radiobiology of Gansu Province, Lanzhou, China

4 College of Animal Science and Technology, Inner Mongolia University for Nationalities, Tong Liao, China

5 University of Chinese Academy of Sciences, Beijing, China

Correspondence to:

Baoquan Zhao, email:

Burong Hu, email:

Keywords: ilomastat, radiation-induced lung injury, pneumonitis, lung fibrosis, MMPs, Pathology Section

Received: April 07, 2017 Accepted: June 05, 2017 Published: June 15, 2017

Abstract

Lung injury is one of the pathological features in human or animal after radiation and the main side effect for patient after lung cancer radiotherapy. The efficient protective strategy still needs to exploit and the underlying mechanisms remain to be investigated. We found that the expression and activity of matrix metalloproteinases (MMPs) significantly increased at the early stage of radiation-induced lung injury (RILI). Pretreatment with Ilomastat, a synthetic inhibitor of MMPs, decreased the expression and activity of MMPs and significantly alleviated the lung inflammation and fibrosis in the irradiated mice, as well as enhanced the survival of irradiated mice. In addition, the levels of TGF-β, IL-6, TNF-α and IL-1β in the tissues dramatically reduced in the irradiated mice pretreated with Ilomastat. Furthermore, our experiments in vitro also showed that radiation significantly increased the MMPs activity, and Ilomastat pretreatment inhibited the activity of MMPs activated by irradiation and increased the cell survival. It is the first report, to our knowledge, to demonstrate that Ilomastat is a potential effective reliever for RILI and MMPs may play important roles in the process of RILI.


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