HIV Increases the Risk of Cigarette Smoke-Induced Emphysema Through MMP-9.
HIV Increases the Risk of Cigarette Smoke-Induced Emphysema Through MMP-9.
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DOI：
10.1097/qai.0000000000003125
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发表时间：
2023-03-01
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HIV 与肺气肿风险增加有关。基质金属蛋白酶 9 (MMP-9) 是一种与肺气肿相关的肺组织重塑酶。我们之前发现 MMP-9 活性随着氧化应激的增加而增加，并且 HIV 会增加肺泡氧化应激。我们假设 HIV 蛋白会增加 MMP-9 引起的香烟烟雾诱发肺气肿的风险。 HIV-1 转基因大鼠和野生型同窝小鼠暴露于香烟烟雾或假烟雾中 8 周。评估肺顺应性和组织学。获得支气管肺泡灌洗液（BAL）、原代肺泡巨噬细胞（AM）和血清样本。将大鼠肺泡巨噬细胞系暴露于 HIV 蛋白 Tat，并通过蛋白质免疫印迹法评估 MMP-9 水平。分别通过 ELISA 和细胞免疫荧光法评估 HIV 大鼠模型 AM 中的 MMP-9 蛋白表达和活性。对患有和不患有 HIV 和烟草依赖的人类受试者的血清进行 MMP-9 水平评估。 Tat 暴露后，大鼠肺泡巨噬细胞中 MMP-9 的表达显着增加。 HIV-1转基因大鼠出现肺气肿，而同窝野生型大鼠则没有。与野生型大鼠相比，暴露于香烟烟雾后的 HIV-1 转基因大鼠的血清、BAL 和 AM 中 MMP-9 的表达也有所增加。与此同时，HIV+吸烟者的血清样本中 MMP-9 水平高于未感染 HIV 和不吸烟的受试者。 HIV 和香烟烟雾的结合会增加实验性大鼠 HIV 模型和人类受试者中 MMP-9 的表达。 HIV 和香烟烟雾都会诱发肺泡氧化应激，从而增加 MMP-9 活性。
HIV is associated with an increased risk for emphysema. Matrix metalloproteinase 9 (MMP-9) is a lung tissue remodeling enzyme associated with emphysema. We previously found MMP-9 activity increases with increases in oxidative stress and that HIV increases alveolar oxidative stress. We hypothesized that HIV proteins would increase the risk of cigarette smoke-induced emphysema due to MMP-9. HIV-1 transgenic rats and wild-type littermates were exposed to cigarette smoke or sham for 8 weeks. Lung compliance and histology were assessed. Bronchoalveolar lavage (BAL), primary alveolar macrophages (AM), and serum samples were obtained. A rat alveolar macrophage cell line was exposed to the HIV protein Tat, and MMP-9 levels were assessed by Western immunoblotting. MMP-9 protein expression and activity were assessed in AM from the HIV rat model by ELISA and cytoimmunofluoresence, respectively. Serum from human subjects with and without HIV and tobacco dependence was assessed for MMP-9 levels. MMP-9 expression was significantly increased in rat alveolar macrophages after Tat exposure. HIV-1 transgenic rats developed emphysema while wild-type littermates did not. MMP-9 expression was also increased in the serum, BAL, and AM of HIV-1 transgenic rats after exposure to cigarette smoke compared with wild-type rats. In parallel, serum samples from HIV+ smokers had higher levels of MMP-9 than subjects without HIV and those who did not smoke. The combination of HIV and cigarette smoke increases MMP-9 expression in experimental rat HIV models and human subjects. HIV and cigarette smoke both induce alveolar oxidative stress and thereby increase MMP-9 activity.