Ionizing radiation enhances matrix metalloproteinase-2 production in human lung epithelial cells
Ionizing radiation enhances matrix metalloproteinase-2 production in human lung epithelial cells
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DOI：
10.1152/ajplung.2001.280.1.l30
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发表时间：
2001-01-01
影响因子：
4.9
通讯作者：
Kobayashi, M
中科院分区：
文献类型：
--
作者：
Araya, J;Maruyama, M;Kobayashi, M
放射性肺炎是放射治疗的主要并发症。然而，详细的细胞机制还没有明确的定义。基于对急性肺损伤时基底膜破裂的认识，以及基质金属蛋白酶-2能降解基底膜的主要成分之一的IV型胶原，我们推测电离辐射会调节人肺上皮细胞产生基质金属蛋白酶-2。为了评估这一点，我们研究了辐射对正常人支气管上皮细胞和A549细胞中基质金属蛋白酶-2的调节作用。用酶谱法检测条件培养液中基质金属蛋白酶-2的活性，用逆转录聚合酶链式反应检测基质金属蛋白酶-2的mRNA水平。这两个细胞都表达72 kDa的明胶溶解活性，对应于基质金属蛋白酶-2，辐射增加了这一活性。与酶谱结果一致的是，电离辐射增加了基质金属蛋白酶-2的mRNA水平。这种辐射诱导的MMP2表达增加是通过P53介导的，因为P53反义寡核苷酸抑制了辐射后A549细胞中MMP2活性的增加和P53的积聚。这些结果表明，人肺上皮细胞表达基质金属蛋白酶-2参与了放射性肺损伤。
Radiation pneumonitis is a major complication of radiation therapy. However, the detailed cellular mechanisms have not been clearly defined. Based on the recognition that basement membrane disruption occurs in acute lung injury and that matrix metalloproteinase (MMP)-2 can degrade type IV collagen, one of the major components of the basement membrane, we hypothesized that ionizing radiation would modulate MMP-2 production in human lung epithelial cells. To evaluate this, the modulation of MMP-2 with irradiation was investigated in normal human bronchial epithelial cells as well as in A549 cells. We measured the activity of MMP-2 in the conditioned medium with zymography and the MMP-2 mRNA level with RT-PCR. Both of these cells constitutively expressed 72-kDa gelatinolytic activity, corresponding to MMP-2, and exposure to radiation increased this activity. Consistent with the data of zymography, ionizing radiation increased the level of MMP-2 mRNA. This radiation-induced increase in MMP-2 expression was mediated via p53 because the p53 antisense oligonucleotide abolished the increase in MMP-2 activity as well as the accumulation of p53 after irradiation in A549 cells. These results indicate that MMP-2 expression by human lung epithelial cells is involved in radiation-induced lung injury.