Active Cushing Disease Is Characterized by Increased Adipose Tissue Macrophage Presence.
Active Cushing Disease Is Characterized by Increased Adipose Tissue Macrophage Presence.
复制标题
DOI：
10.1210/jc.2018-02552
复制
发表时间：
2019-06
期刊：
影响因子：
--
通讯作者：
Irene T. Lee;Alexandria Atuahene;H. E. Eğritağ;Ling Wang;M. Donovan;C. Buettner;E. Geer
中科院分区：
文献类型：
--
作者：
Irene T. Lee;Alexandria Atuahene;H. E. Eğritağ;Ling Wang;M. Donovan;C. Buettner;E. Geer
背景：尽管糖皮质激素(GCs)具有强大的抗炎作用，但库欣病(CD)引起的皮质醇增多症患者循环中促炎症细胞因子增加，这可能与他们的胰岛素抵抗和心血管疾病有关。CD患者全身炎症增加的机制和组织尚不清楚。目的探讨慢性镉致内源性GC暴露与人体脂肪组织(AT)炎症的关系。设计、环境、参与者来自10名CD活动期患者和10名年龄、性别和体重指数匹配的健康受试者的腹部皮下AT样本被评估巨噬细胞的浸润和促炎细胞因子的mRNA表达。主要观察指标采用免疫组织化学方法检测AT组织中波形蛋白、caspase、CD3、CD4、CD8、CD11c、CD20、CD31、CD56、CD68、CD163的表达。定量聚合酶链式反应检测精氨酸酶、CD11b、CD68、EMR-1、IL-6、IL-10、单核细胞趋化蛋白-1和肿瘤坏死因子-α的基因表达。结果CD活动期患者AT中CD68+巨噬细胞和CD4+T淋巴细胞的平均百分率高于对照组，CD11c+M1巨噬细胞的平均面积增加，CD11c+冠状结构的数量增加，波形蛋白减少。聚合酶链式反应显示CD患者中所有分析标记物的mRNA表达均无差异。结论慢性镉暴露于GCs可增加AT巨噬细胞的存在，这是AT炎症的一个标志。因此，AT炎症可能是CD全身性炎症的来源，进而可能导致这些患者的肥胖、胰岛素抵抗和心血管疾病。
CONTEXT Although glucocorticoids (GCs) have potent anti-inflammatory actions, patients with hypercortisolism due to Cushing disease (CD) have increased circulating proinflammatory cytokines that may contribute to their insulin resistance and cardiovascular disease. The mechanisms and tissues that account for the increased systemic inflammation in patients with CD are unknown. OBJECTIVE To determine whether chronic endogenous GC exposure due to CD is associated with adipose tissue (AT) inflammation in humans. DESIGN, SETTING, PARTICIPANTS Abdominal subcutaneous AT samples from 10 patients with active CD and 10 age-, sex-, and body mass index‒matched healthy subjects were assessed for macrophage infiltration and mRNA expression of proinflammatory cytokines. MAIN OUTCOME MEASURE Using immunohistochemistry, AT samples were analyzed for the expression of vimentin, caspase, CD3, CD4, CD8, CD11c, CD20, CD31, CD56, CD68, and CD163. Quantitative PCR was used to assess the mRNA gene expression of arginase, CD11b, CD68, EMR-1, IL-6, IL-10, MCP-1, and TNF-α. RESULTS Immunohistochemistry revealed higher mean percentage infiltration of CD68+ macrophages and CD4+ T lymphocytes, increased mean area of CD11c+ M1 macrophages, higher number of CD11c+ crownlike structures, and decreased vimentin in the AT of patients with active CD compared with controls. PCR revealed no differences in mRNA expression of any analyzed markers in patients with CD. CONCLUSIONS Chronic exposure to GCs due to CD increases the presence of AT macrophages, a hallmark of AT inflammation. Hence, AT inflammation may be the source of the systemic inflammation seen in CD, which in turn may contribute to obesity, insulin resistance, and cardiovascular disease in these patients.