Chlamydia pneumoniae induces macrophage-derived foam cell formation by up-regulating acyl-coenzyme A: cholesterol acyltransferase 1
Chlamydia pneumoniae induces macrophage-derived foam cell formation by up-regulating acyl-coenzyme A: cholesterol acyltransferase 1
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肺炎衣原体通过上调酰基辅酶 A：胆固醇酰基转移酶 1 诱导巨噬细胞衍生的泡沫细胞形成
DOI：
10.1016/j.micinf.2008.11.001
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发表时间：
2009-02-01
影响因子：
5.8
通讯作者：
Wan, Jingjing
中科院分区：
文献类型：
--
作者：
He, Ping;Mei, Chunli;Wan, Jingjing
在巨噬细胞中，酰基辅酶 A：胆固醇酰基转移酶 1 (ACAT1) 合成的胆固醇酯的积累在泡沫细胞形成中发挥着至关重要的作用，泡沫细胞是早期动脉粥样硬化病变的标志。表明肺炎衣原体（C.pneumoniae）诱导泡沫细胞形成。然而，肺炎衣原体诱导泡沫细胞形成的机制尚未完全阐明。在这项研究中，我们发现肺炎衣原体在暴露于低密度脂蛋白（LDL）的THP-1衍生巨噬细胞中以剂量依赖性方式增加酰基辅酶A：胆固醇酰基转移酶1（ACAT1）mRNA和蛋白质的表达。此外，肺炎衣原体剂量依赖性地抑制过氧化物酶体增殖物激活受体γ（PPARγ）mRNA和蛋白的表达。罗格列酮是一种特异性 PPAR γ 激动剂，不仅能剂量依赖性地减轻肺炎衣原体感染引起的 PPAR γ 表达下调，而且还能剂量依赖性地抑制肺炎衣原体诱导的 ACAT1 表达。此外，从形态学（油红O染色）和生物化学（酶化学方法）标准来看，较高剂量的罗格列酮（10和20μM）抑制了肺炎衣原体诱导的泡沫细胞形成。这些结果首先证明肺炎衣原体通过 PPAR γ 依赖性途径上调 ACAT1 表达来诱导巨噬细胞衍生的泡沫细胞形成，这可能有助于其促动脉粥样硬化特性。 (C) 2008 Elsevier Masson SAS。版权所有。
In macrophages, the accumulation of cholesteryl esters synthesized by acyl-coenzyme A: cholesterol acyltransferase 1(ACAT1) plays a crucial role in foam cell formation, a hallmark of early atherosclerotic lesions. It is suggested that Chlamydia pneumoniae (C. pneumoniae) induces foam cell formation. However, the mechanism of foam cell formation induced by C. pneumoniae has not been fully elucidated. In this study, we found that C. pneumoniae increased the expression of acyl-coenzyme A: cholesterol acyltransferase 1(ACAT1) mRNA and protein in a dose-dependent manner in THP-1-derived macrophages exposed to low density lipoprotein (LDL). In addition, C. pneumoniae dose-dependently suppressed the expression of peroxisome proliferator-activated receptor gamma (PPAR gamma) mRNA and protein. Rosiglitazone, a specific PPAR gamma agonist, not only dose-dependently alleviated the down-regulation of PPAR gamma expression by C. pneumoniae infection, but also dose-dependently inhibited the C. pneumoniae-induced ACAT1 expression. Furthermore, higher doses of rosiglitazone (10 and 20 mu M) suppressed the C. pneumoniae-induced foam cell formation from morphological (Oil red O staining) and biochemical (zymochemistry method) criteria. These results first demonstrate that C. pneumoniae induces macrophage-derived foam cell formation by up-regulating ACAT1 expression via PPAR gamma-dependent pathway, which may contribute to its pro-atherogenic properties. (C) 2008 Elsevier Masson SAS. All rights reserved.