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体外人脂肪组织中白细胞介素8产生及基因表达的调控

Regulation of interleukin 8 production and gene expression in human adipose tissue in vitro.

作者信息

Bruun J M, Pedersen S B, Richelsen B

机构信息

Department of Endocrinology and Metabolism C, Aarhus Amtssygehus, Aarhus University Hospital and Faculty of Health Sciences, Aarhus University, DK-8000 Aarhus C, Denmark.

出版信息

J Clin Endocrinol Metab. 2001 Mar;86(3):1267-73. doi: 10.1210/jcem.86.3.7264.

DOI:10.1210/jcem.86.3.7264
PMID:11238519
Abstract

A variety of cytokines and other compounds are produced in the human adipose tissue and may have autocrine functions in the adipose tissue as well as be involved in the complications seen in association with obesity. Because it recently has been reported that interleukin 8 (IL-8), through its effects on the macrophage and endothelial cell, may be involved in the pathogenesis of atherosclerosis, we found it of interest to investigate whether IL-8 is produced in human adipose tissue in vitro. Human sc adipose tissue was investigated both in incubations with whole adipose tissue fragments as well as with isolated mature adipocytes. In adipose tissue fragments, IL-1beta (3 nM) and tumor necrosis factor alpha (0.6 nM) were able to stimulate IL-8 production by 12-fold and 5-fold, respectively (P < 0.001), when incubated for 48 h. Incubations with isolated adipocytes were performed up to 6 h, and IL-1beta and tumor necrosis factor alpha significantly increased IL-8 production by 50-60% (P < 0.05). Dexamethasone (50 nM) decreased IL-8 production from adipose tissue fragments by 57% (P < 0.01) and from adipocytes by 37% (P < 0.05). IL-8 messenger RNA expression in adipocytes incubated with IL-1beta was increased already after 2 h (P < 0.05). Thus, the effect of proinflammatory cytokines and dexamethasone on IL-8 production in adipose tissue seems to be mediated at the transcriptional level. In conclusion, it is demonstrated for the first time that IL-8 is produced and released from human adipose tissue and from isolated adipocytes in vitro, which may indicate that IL-8 from adipose tissue could be involved in some of the obesity-related complications.

摘要

人体脂肪组织会产生多种细胞因子和其他化合物,这些物质在脂肪组织中可能具有自分泌功能,并且与肥胖相关的并发症有关。由于最近有报道称,白细胞介素8(IL-8)通过对巨噬细胞和内皮细胞的作用,可能参与动脉粥样硬化的发病机制,因此我们有兴趣研究IL-8是否在体外人体脂肪组织中产生。我们对人体皮下脂肪组织进行了研究,采用了完整脂肪组织片段以及分离的成熟脂肪细胞进行培养。在脂肪组织片段中,当孵育48小时时,白细胞介素1β(IL-1β,3 nM)和肿瘤坏死因子α(TNF-α,0.6 nM)分别能够刺激IL-8的产生增加12倍和5倍(P < 0.001)。对分离的脂肪细胞进行长达6小时的孵育,IL-1β和TNF-α显著增加IL-8的产生达50 - 60%(P < 0.05)。地塞米松(50 nM)使脂肪组织片段中的IL-8产生减少57%(P < 0.01),使脂肪细胞中的IL-8产生减少37%(P < 0.05)。与IL-1β孵育的脂肪细胞中,IL-8信使核糖核酸(mRNA)表达在2小时后就已增加(P < 0.05)。因此,促炎细胞因子和地塞米松对脂肪组织中IL-8产生的影响似乎是在转录水平介导的。总之,首次证明IL-8在体外可从人体脂肪组织和分离的脂肪细胞中产生并释放,这可能表明来自脂肪组织的IL-8可能参与了一些与肥胖相关的并发症。

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