Cardiology Unit and Atherosclerosis Research Unit, Department of Medicine, Karolinska University Hospital, Solna, Stockholm, Sweden.
Am J Physiol Endocrinol Metab. 2010 Aug;299(2):E234-40. doi: 10.1152/ajpendo.00115.2010. Epub 2010 May 18.
Adipose tissue (AT) is a store of energy but also an endocrine organ with the capacity to produce and release proinflammatory mediators into the circulation. The mechanism that may trigger human AT inflammation on a cellular level still remains largely unknown. The aim of this study was to investigate whether an acute systemic inflammation increases AT inflammatory activity, focused on innate immunity. Open heart surgery results in an extensive acute systemic inflammation. Therefore, we investigated the in vivo gene expression and production of inflammatory mediators in omental and subcutaneous AT stimulated by surgery. Biopsies from omental and subcutaneous AT were collected before and after cardiopulmonary bypass. Blood samples were collected at the same time as the AT biopsies and plasma IL-6 levels were measured with ELISA. RT-PCR was used for quantification of relative AT gene expression. To verify the gene expression results on a protein level, we used immunohistochemistry and microdialysis. After surgery, in both omental and subcutaneous AT, there was a strong upregulation of nuclear factor-kappaB-regulated genes, e.g., chemokine ligand-2, E-selectin, IL-1beta, IL-6, IL-8, and Toll-like receptor-2. Immunohistochemistry showed staining for E-selectin associated with a high number of macrophages in close contact with and in the vascular wall. Increased levels of IL-6 were detected in microdialysate from subcutaneous AT. In conclusion, we present the novel finding that this model of inflammation induced a strong inflammatory response in both omental and subcutaneous AT including adhesion of macrophages to an activated endothelium and release of IL-6 from AT interstitium. It can be hypothesized that AT exerts a modulatory effect on innate immunity in humans.
脂肪组织（AT）是能量的储存库，但也是具有产生和释放促炎介质进入循环能力的内分泌器官。触发人类 AT 炎症的细胞机制在很大程度上仍然未知。本研究旨在研究急性全身炎症是否会增加 AT 的炎症活性，重点关注先天免疫。心脏直视手术会导致广泛的急性全身炎症。因此，我们研究了手术刺激网膜和皮下 AT 中先天免疫的体内基因表达和炎症介质的产生。在体外循环之前和之后从网膜和皮下 AT 采集活检。同时采集 AT 活检时的血液样本，并使用 ELISA 测量血浆 IL-6 水平。RT-PCR 用于定量相对 AT 基因表达。为了在蛋白质水平上验证基因表达结果，我们使用了免疫组织化学和微透析。手术后，网膜和皮下 AT 中核因子-κB 调节基因（如趋化因子配体-2、E-选择素、IL-1β、IL-6、IL-8 和 Toll 样受体-2）的表达均明显上调。免疫组织化学显示 E-选择素染色与大量巨噬细胞密切接触并位于血管壁中。从皮下 AT 的微透析液中检测到 IL-6 水平升高。总之，我们提出了新的发现，即这种炎症模型在网膜和皮下 AT 中引起了强烈的炎症反应，包括巨噬细胞与激活的内皮细胞黏附和 AT 间质中 IL-6 的释放。可以假设 AT 对人类的先天免疫具有调节作用。
