Expression of matrix metalloproteinases subsequent to urogenital Chlamydia muridarum infection of mice.
Expression of matrix metalloproteinases subsequent to urogenital Chlamydia muridarum infection of mice.
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小鼠泌尿生殖道衣原体感染后基质金属蛋白酶的表达。
DOI：
10.1128/iai.73.10.6962-6973.2005
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发表时间：
2005
影响因子：
3.1
通讯作者：
Cohoon,KP
中科院分区：
文献类型：
--
作者：
Ramsey,KH;Sigar,IM;Schripsema,JH;Shaba,N;Cohoon,KP
这项研究的中心假设是，小鼠衣原体感染后基质金属蛋白酶（MMP）会增强，并且它们的表达在小鼠品系中会有所不同，这些小鼠品系对慢性衣原体引起的疾病的易感性不同。为了验证这一假设，雌性 C3H/HeN 和 C57BL/6 小鼠阴道内感染鼠衣原体。评估子宫和输卵管组织的 MMP 基因及其组织抑制剂的转录。与 C57BL/6 小鼠相比，在 C3H/HeN 小鼠中观察到 MMP 基因相对于感染前组织的活性增加。使用明胶酶谱法，我们检测到两种小鼠品系的组成型 MMP-2 活性，但 MMP-9 有所增加。酪蛋白酶谱表明存在两种与 MMP-12 和可能与 MMP-7 一致的弹性蛋白酶样活性。蛋白质印迹和抗原捕获酶联免疫测定也证实，两种小鼠品系感染后，MMP-9 表达增加，但组成型 MMP-2 表达增加。在 C57BL/6 小鼠中，在整个 56 天的监测期内，MMP-9 以单体和二聚体形式存在。 C3H/HeN 小鼠产生二聚体 MMP-9，但在第 14 天也观察到单体形式的增加。两种品系之间 MMP-9 的翻译后修饰也不同。免疫组织化学显示，中性粒细胞是两种小鼠品系中 MMP-9 的重要来源。我们得出的结论是，MMP（特别是 MMP-9）的相对表达和活性存在差异，发生在对慢性衣原体疾病的易感性不同的小鼠中。这些差异可能导致该疾病的慢性后遗症产生不同的结果。
The central hypothesis of this study was that matrix metalloproteinases (MMPs) would be enhanced following murine chlamydial infection and that their expression would vary in mouse strains that differ in their susceptibility to chronic chlamydia-induced disease. To address this hypothesis, female C3H/HeN and C57BL/6 mice were infected intravaginally withChlamydia muridarum. Uterine and oviduct tissues were assessed for transcription of MMP genes and their tissue inhibitors. An increased activity of MMP genes relative to preinfection tissues was observed in the C3H/HeN mice when compared to C57BL/6 mice. Using gelatin zymography, we detected constitutive MMP-2 activity in both strains of mice but an increase in MMP-9. Casein zymography indicated the presence of two elastase-like activities consistent with MMP-12 and possibly MMP-7. Western blotting and antigen capture enzyme-linked immunoassay also confirmed an increase in MMP-9 but constitutive MMP-2 expression subsequent to the infection in both strains of mice. In C57BL/6 mice, MMP-9 was present in monomer and dimer form throughout the 56-day monitoring period. C3H/HeN mice produced dimeric MMP-9, but increases in the monomer form were also observed through day 14. Post-translational modification of MMP-9 between the two strains also differed. Immunohistochemistry revealed neutrophils as a prominent source for MMP-9 in both strains of mice. We conclude that differences in the relative expression and activity of MMPs, particularly MMP-9, occur in mice differing in their susceptibility to the development of chronic chlamydial disease. These differences may account for disparate outcomes with regard to chronic sequelae of the disease.