Macrophage antioxidant enzymes regulate Chlamydia pneumoniae chronicity:: Evidence of the effect of redox balance on host-pathogen relationship

Macrophage antioxidant enzymes regulate Chlamydia pneumoniae chronicity:: Evidence of the effect of redox balance on host-pathogen relationship
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DOI:
10.1016/j.imbio.2005.12.001
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发表时间:
2006-01-01
期刊:
影响因子:
2.8
通讯作者:
Chaudhry, Abir
Chaudhry, Abir
中科院分区:
医学4区
文献类型:
--
作者:
Azenabor, Anthony A.;Muili, Kamaldeen;Chaudhry, Abir

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肺炎衣原体的潜伏期、慢性化和复发性是其生物学特性,在肺炎衣原体与宿主相互作用的过程和结果中起着核心作用。由于氧化还原状态通过分子信号机制直接反映炎症反应,因此我们决定研究巨噬细胞氧化还原平衡对肺炎衣原体慢性化分子指标的调节作用。我们检测了GSH-GSSG状态、抗氧化酶(SOD、GPX和γ-GCS)的活性及其蛋白和基因表达、MOMP和cHSP-60的蛋白和基因表达,以及氧化还原平衡对建立巨噬细胞生产性感染的影响。结果表明,肺炎衣原体可引起巨噬细胞GSH-GSSG水平、抗氧化酶活性、mRNA基因和蛋白表达的变化。这与巨噬细胞中肺炎衣原体的状态和状态的相关性通过抑制物诱导的抗氧化酶的衰减来评估,并且有证据表明,虽然SOD的衰减对MOMP和cHSP-60的基因和蛋白表达没有显著的影响,但伽马-GCS的衰减增加了cHSP-60的基因和蛋白的表达。慢性肺炎衣原体(cHSP-60)分子证据的增加与正常肺炎衣原体的减少是一致的。这些发现反映了氧化还原平衡调节对巨噬细胞肺炎衣原体感染结局的重要性,这是衣原体疾病发病机制中的一个重要过程。(C)2006年爱思唯尔股份有限公司。版权所有。
Latency, chronicity and recurrent nature are the features of Chlamydia pneumoniae biology which play a central role in the course and outcome of C pneumoniae-host interaction. Since redox status is directly an indicator of inflammatory response via molecular signaling mechanisms, we decided to study the regulatory role of macrophage cellular redox balance on the molecular indices of C pneumoniae chronicity. We examined GSH-GSSG status, the activities of antioxidant enzymes (SOD, GPx and gamma-GCS), along with their protein and gene expression, the MOMP and cHSP-60 protein and gene expression, and the consequence of redox balance on the establishment of productive infection in macrophages. Results showed that C pneumoniae caused changes in GSH-GSSG levels, antioxidant enzymes activity, mRNA gene and protein expression in macrophages. The relevance of this to the state and status of C pneumoniae in macrophages was assessed by inhibitor induced attenuation of antioxidant enzymes and there was evidence that, while SOD attenuation did not significantly affect MOMP and cHSP-60 gene and protein expression, gamma-GCS attenuation increased cHSP-60 gene and protein expression. The increase in molecular evidence of chronic forms of C pneumoniae (cHSP-60) was consistent with decrease in normal forms of C pneumoniae. These findings reflect the importance of redox balance modulation on the outcome of C pneumoniae infection in macrophages, a significant process in the pathogenesis of chlamydial diseases. (c) 2006 Elsevier GmbH. All rights reserved.