Adiponectin and Functional Adiponectin Receptor 1 Are Expressed by Airway Epithelial Cells in Chronic Obstructive Pulmonary Disease
Adiponectin and Functional Adiponectin Receptor 1 Are Expressed by Airway Epithelial Cells in Chronic Obstructive Pulmonary Disease
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DOI：
10.4049/jimmunol.182.1.684
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发表时间：
2009-01-01
影响因子：
4.4
通讯作者：
Broide, David H.
中科院分区：
文献类型：
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作者：
Miller, Marina;Cho, Jae Youn;Broide, David H.
我们使用120 Ab细胞因子阵列筛选COME（慢性阻塞性肺疾病-肺气肿）和对照受试者的支气管肺泡灌洗液（BAL），并证明脂联素在COME的BAL中高度表达。脂联素ELISA证实，与吸烟者和健康对照组相比，COME中脂联素在BAL中高度表达。COME受试者肺切片的免疫组织化学研究表明，气道上皮细胞表达显着水平的脂联素和脂联素受体（AdipoR）I，但不AdipoR 2。在体外研究中，纯化的人肺A549上皮细胞的群体表明，他们表达脂联素和AdipoR I（但不AdipoR 2），如通过RT-PCR，蛋白质印迹和免疫组化评估。肺A549上皮细胞AdipoR 1与脂联素孵育诱导IL-8的释放，这被AdipoR 1的小干扰RNA抑制。使用小鼠COPD模型，烟草烟雾暴露诱导COPD的证据以及BAL液中脂联素水平的增加和气道上皮细胞脂联素表达的增加。由于脂联素在脂肪细胞中的表达依赖于NF-κ B，我们测定了暴露于烟草烟雾的CC 10-Cre（tg）/Ikk β（Delta/Delta）小鼠（缺乏激活气道上皮中NF-κ B的能力）中的脂联素水平。这些研究表明，CC 10-Cre（tg）/Ikk β（Delta/Delta）和野生型小鼠具有相似水平的BAL脂联素和气道上皮脂联素免疫染色。总之，这些研究证实了脂联素和功能性AdipoR 1由肺上皮细胞表达的新观察结果，表明脂联素激活COME中上皮细胞的潜在自分泌和/或旁分泌途径。免疫学杂志，2009，182：684-691.
We screened bronchoalveolar lavage (BAL) fluids from COME (chronic obstructive pulmonary disease-Emphysema) and control subjects using a 120 Ab cytokine array and demonstrated that adiponectin was highly expressed in BAL in COME. An adiponectin ELISA confirmed that adiponectin was highly expressed in BAL in COME compared with smokers and healthy control subjects. Immunohistochemistry studies of lung sections from subjects with COME demonstrated that airway epithelial cells expressed significant levels of adiponectin and adiponectin receptor (AdipoR) I but not AdipoR2. In vitro studies with purified populations of human lung A549 epithelial cells demonstrated that they expressed both adiponectin and AdipoR I (but not AdipoR2) as assessed by RT-PCR, Western blot, and immunohistochemistry. Lung A549 epithelial AdipoR1 were functional as incubation with adiponectin induced release of IL-8, which was inhibited by small interfering RNA to AdipoR1. Using a mouse model of COPD, tobacco smoke exposure induced both evidence of COPD as well as increased levels of adiponectin in BAL fluid and increased adiponectin expression by airway epithelial cells. As adiponectin expression in adipocytes is dependent upon NF-kappa B we determined levels of adiponectin in tobacco smoke exposed CC10-Cre(tg)/Ikk beta(Delta/Delta) mice (deficient in the ability to activate NF-kappa B in airway epithelium). These studies demonstrated that CC10-Cre(tg)/Ikk beta(Delta/Delta) and wild-type mice had similar levels of BAL adiponectin and airway epithelial adiponectin immunostaining. Overall, these studies demonstrate the novel observation that adiponectin and functional AdipoR1 are expressed by lung epithelial cells, suggesting a potential autocrine and/or paracrine pathway for adiponectin to activate epithelial cells in COME. The Journal of Immunology, 2009, 182: 684-691.