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Expression of Matrix Metalloproteinases Subsequent to Urogenital Chlamydia muridarum Infection of Mice

机译:泌尿生殖系统衣原体感染小鼠后基质金属蛋白酶的表达

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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 with Chlamydia 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.
机译:这项研究的中心假设是,鼠衣原体感染后基质金属蛋白酶(MMPs)会增强,并且它们在小鼠菌株中的表达会有所不同,这些小鼠菌株对慢性衣原体诱发疾病的敏感性不同。为了解决这个假设,将雌性C3H / HeN和C57BL / 6小鼠阴道内感染了 muridrum muridarum 。评估子宫和输卵管组织中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,我们检测到这两种小鼠品系中的组成性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甚至可能与MMP-7一致的弹性蛋白酶样活性。 Western印迹和抗原捕获酶联免疫测定法还证实,两种小鼠感染后,MMP-9均增加,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小鼠产生了二聚体MMP-9,但是直到第14天也观察到单体形式的增加。两种菌株之间MMP-9的翻译后修饰也不同。免疫组织化学显示,嗜中性粒细胞是这两种小鼠中MMP-9的主要来源。我们得出结论,MMPs,尤其是MMP-9的相对表达和活性的差异发生在小鼠中,它们对慢性衣原体疾病的敏感性不同。这些差异可以解释关于该疾病的慢性后遗症的不同结果。

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