Effects of norepinephrine, HIV type 1 infection, and leukocyte interactions with endothelial cells on the expression of matrix metalloproteinases.
Effects of norepinephrine, HIV type 1 infection, and leukocyte interactions with endothelial cells on the expression of matrix metalloproteinases.
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去甲肾上腺素、HIV 1 型感染以及白细胞与内皮细胞相互作用对基质金属蛋白酶表达的影响。
DOI：
10.1089/088922201753342013
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Ansari,AA
中科院分区：
文献类型：
--
作者：
Sundstrom,JB;Mosunjac,M;Martinson,DE;Bostik,P;Donahoe,RM;Gravanis,MB;Ansari,AA
在体外培养模型中检测了与艾滋病相关心肌病和可卡因滥用相关的基质金属蛋白酶（MMPs）的表达。将HIV感染或未感染的人外周血单核细胞（PBMCs）与原代人心脏微血管内皮细胞（hmvecc）在存在或不存在可卡因诱导的儿茶酚胺去甲肾上腺素（NE）的情况下共培养。通过酶联免疫吸附法检测培养上清中MMP-1、-2、-3、-7、-9和-13的含量，以及金属蛋白酶1 （TIMP-1）和TIMP-2的组织抑制剂含量。在hvec和pbmc的个体培养中检测到低水平的组成性表达MMP-1和-2。NE没有诱导hmvec表达MMP或TIMP，但在未感染的pbmc中，MMP-1和-2的表达适度增加（3- 4倍）。在hmvec和未感染的pbmc共培养中检测到ne诱导的MMP-1（5倍）和MMP -2（15倍）水平升高。HIV感染可增强pbmc的MMP-1（46倍）和MMP-2（48倍）以及活性MMP-7（33倍）和MMP-9（50倍）。hiv感染的pbmc与hmvec共培养增加了MMP-1（110倍）和MMP-2（307倍），但没有活性的MMP-7和-9。NE、HIV感染和共培养的组合增加了MMP-1（126倍）和MMP-2（467倍），活性MMP-7（65倍）和MMP-9（75倍）。在任何治疗组中均未检测到MMP-3或13，TIMP-1和-2与观察到的MMPs水平成反比。这些结果表明，HIV感染、NE和白细胞内皮相互作用在与艾滋病相关心肌病相关的TIMPs和MMPs表达调控中表现出单独和重叠的协同作用。
The expression of matrix metalloproteinases (MMPs) associated with AIDS-related cardiomypathies and cocaine abuse was examined in anin vitrococulture model. Human peripheral blood mononuclear cells (PBMCs), HIV infected or uninfected, were placed in coculture with primary human cardiac microvascular endothelial cells (HMVEC-C) in the presence or absence of the cocaine-inducible catecholamine norepinephrine (NE). Culture supernatants were assayed for MMP-1, -2, -3, -7, -9, and -13, and for tissue inhibitor of metalloproteinase 1 (TIMP-1) and TIMP-2, by enzyme-linked immunosorbent assay. Low levels of constitutively expressed MMP-1 and -2 were detected in individual cultures of HMVEC-C and PBMCs. NE did not induce MMP or TIMP expression by HMVEC-C and caused modest increases (3- to 4-fold) in MMP-1 and -2 by uninfected PBMCs. Increased levels of NE-induced MMP-1 (5-fold) and MMP -2 (15-fold) were detected in cocultures of HMVEC-C and uninfected PBMCs. HIV infection enhanced MMP-1 (46-fold) and MMP-2 (48-fold) and active MMP-7 (33-fold) and MMP-9 (50-fold) by PBMCs. Coculture of HIV-infected PBMCs with HMVEC-C increased MMP-1 (110-fold) and MMP-2 (307-fold) but not active MMP-7 and -9. The combination of NE, HIV infection, and coculture increased MMP-1 (126-fold) and MMP-2 (467-fold), and active MMP-7 (65-fold) and MMP-9 (75-fold). MMP-3 or-13 was not detected in any of the treatment groups and TIMP-1 and -2 appeared inversely proportional to the observed levels of MMPs. These results suggest that HIV infection, NE, and leukocyte endothelial interactions demonstrate separate and overlapping cooperative effects on the regulation of expression of TIMPs and MMPs associated with AIDS-related cardiomyopathies.