Modulation of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in RAW264.7 cells by irradiation.
Modulation of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in RAW264.7 cells by irradiation.
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DOI：
10.3892/mmr.2010.326
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发表时间：
2010-09
影响因子：
3.4
通讯作者：
Y. Zhou;L. Xia;Z. He;W. Ouyang;H. Z;C. Xie
中科院分区：
文献类型：
--
作者：
Y. Zhou;L. Xia;Z. He;W. Ouyang;H. Z;C. Xie
放射性肺损伤是影响患者生活质量的严重并发症。虽然该过程的病理生理学尚未完全了解，但我们假设它可能与巨噬细胞及其分泌的基质金属蛋白酶-9（MMP-9）有关。巨噬细胞是一种炎性细胞，可合成数百种生物活性物质和酶。MMP-9与基底膜的维持密切相关，并导致肺内细胞外基质沉积增加，这是辐射诱导的肺纤维化的特征。我们研究了电离辐射在调节巨噬细胞系中MMP-9的产生中的作用。用不同剂量的γ射线照射RAW264.7细胞，测定不同时间点MMP-9和TIMP-1的表达。RT-PCR结果显示，MMP-9 mRNA水平在照射后24 h达到高峰，48 h开始下降。而TIMP-1 mRNA在照射后24 h仅略有增加，48 h达到显著水平。蛋白质印迹分析表明，照射后细胞中MMP-9蛋白表达增加，而TIMP-1蛋白水平无显着变化。地塞米松可抑制电离辐射诱导的MMP-9蛋白表达增加。提示RAW264.7细胞MMP-9的表达及MMP-9与TIMP-1的失衡可能参与了放射性肺损伤的发生。
Radiation-induced pulmonary injury is a severe complication affecting the quality of life of patients. Although the pathophysiology of the process is not fully understood, we hypothesized that it is potentially related to macrophages and their secretion of matrix metalloproteinase-9 (MMP-9). Macrophages are a type of inflammatory cell that synthesize hundreds of bioactive substances and enzymes. MMP-9 is closely involved in the maintenance of the basilar membrane, and leads to increased extracellular matrix deposition within the lung, which is a characteristic feature of radiation-induced lung fibrosis. We examined the role of ionizing radiation in modulating the production of MMP-9 in a macrophage cell line. RAW264.7 cells were irradiated with various doses of γ-rays, and then MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels were determined at several time points. RT-PCR revealed a marked increase in the levels of MMP-9 mRNA, which peaked at 24 h post-irradiation and had begun to decline by 48 h. By contrast, TIMP-1 mRNA experienced only a slight increase at 24 h post-irradiation, reaching significance at 48 h post-irradiation. Western blot analysis demonstrated an increased expression of MMP-9 protein in the irradiated cells, while TIMP-1 protein levels were not notably changed. Dexamethasone inhibited the increased expression of MMP-9 protein induced by ionizing radiation. These results indicate that MMP-9 expression by RAW264.7 cells, and an imbalance between MMP-9 and TIMP-1, may be involved in radiation-induced lung injury.