期刊
ONCOTARGET
卷 8, 期 37, 页码 60789-60808出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.18487
关键词
ilomastat; radiation-induced lung injury; pneumonitis; lung fibrosis; MMPs; Pathology Section
资金
- National Key Scientific Instrument and Equipment Development Project of China [2012YQ03014210, 2012YQ03014211]
- National Natural Science Foundation of China [U1432121, 81173572]
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-beta, IL-6, TNF-alpha and IL-1 beta 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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