Epithelial and bacterial metalloproteinases and their inhibitors in H-pylori infection of human gastric cells
Epithelial and bacterial metalloproteinases and their inhibitors in H-pylori infection of human gastric cells
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DOI：
10.1152/ajpgi.2001.281.3.g823
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发表时间：
2001-09-01
影响因子：
4.5
通讯作者：
Smolka, AJ
中科院分区：
文献类型：
--
作者：
Göoz, M;Göoz, P;Smolka, AJ
为验证幽门螺杆菌对胃细胞分泌基质金属蛋白酶(MMPs)及其抑制物(TIMPs)的调节作用，对感染和未感染的人胃腺癌(AGS)细胞的培养上清液进行了酶谱分析、基质金属蛋白酶活性测定和免疫印迹分析。AGS细胞分泌明胶溶解活性(尤其是90 kDa)和酪蛋白溶解活性(110 KDa)，以及MMP1、MMP3和TIMP-1、TIMP-2、TIMP-3亚型。幽门螺杆菌分泌酪蛋白溶解活性(60 KDa)、基质金属蛋白酶-3样酶活性和TIMP-3免疫反应。幽门螺杆菌感染增加了110 kDa的酪蛋白溶解活性，并诱导了新的明胶(接近35 kDa)和酪蛋白溶解(22 KDa)活性。感染还增加了基质金属蛋白酶-1和基质金属蛋白酶-3的基础分泌和活化，增加了基质金属蛋白酶-3的分泌，增加了基质金属蛋白酶-3/基质金属蛋白酶-3复合体的形成。TIMP-1和TIMP-2分泌无明显变化。正常AGS细胞呈TIMP-3的全细胞分布，幽门螺杆菌感染后TIMP-3免疫反应向细菌附着部位重新分布。结果表明，幽门螺杆菌感染可调节AGS细胞分泌MMP3和TIMP，而宿主MMP3和Hp表达的TIMP-3同源物至少部分介导了宿主细胞对感染的反应。
To test the hypothesis that Helicobacter pylori regulates gastric cell secretion of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), culture media from infected and uninfected human gastric adenocarcinoma (AGS) cells were analyzed by zymography, MMP activity assays, and immunoblotting. AGS cells secreted gelatinolytic (prominently 90 kDa) and caseinolytic (110 kDa) activity together with MMP-1, MMP-3, and TIMP-1, TIMP-2, and TIMP-3 isoforms. H. pylori secreted caseinolytic activity (60 kDa), MMP-3-like enzyme activity, and TIMP-3 immunoreactivity. H. pylori infection increased the 110-kDa caseinolytic activity and induced new gelatinolytic (similar to 35 kDa) and caseinolytic (22 kDa) activities. Infection also increased both basal secretion and activation of MMP-1 and MMP-3, enhanced TIMP-3 secretion, and increased the formation of MMP-3/TIMP-3 complexes. TIMP-1 and TIMP-2 secretion were unchanged. Normal AGS cells showed a pancellular distribution of TIMP-3, with redistribution of immunoreactivity toward sites of bacterial attachment after H. pylori infection. The data indicate that MMP and TIMP secretion by AGS cells is modulated by H. pylori infection and that host MMP-3 and a TIMP-3 homolog expressed by H. pylori mediate at least part of the host cell response to infection.