Hypoxia-induced inflammatory cytokine secretion in human adipose tissue stromovascular cells.
Hypoxia-induced inflammatory cytokine secretion in human adipose tissue stromovascular cells.
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缺氧诱导的人脂肪组织间质血管细胞中的炎性细胞因子分泌。
DOI：
10.1007/s00125-011-2103-y
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发表时间：
2011-06
期刊：
影响因子：
8.2
通讯作者：
Marks, D. L.
中科院分区：
文献类型：
--
作者：
O'Rourke, R. W.;White, A. E.;Metcalf, M. D.;Olivas, A. S.;Mitra, P.;Larison, W. G.;Cheang, E. C.;Varlamov, O.;Corless, C. L.;Roberts, C. T., Jr.;Marks, D. L.
尽管人类脂肪组织对缺氧的炎症反应尚不清楚，但缺氧被认为是肥胖症脂肪组织炎症的一个原因。本研究的目的是确定人体脂肪组织对缺氧的体外炎症反应，并确定缺氧诱导炎症的分子机制。使用实时定量 PCR、ELISA、蛋白质印迹、免疫荧光显微镜、流式细胞术和免疫组织化学，在体外缺氧培养系统中研究了来自肥胖和瘦人的内脏 (VAT) 和皮下 (SAT) 脂肪组织外植体以及纯化的基质血管细胞 (SVF) 的炎症环境和反应。肥胖的人体脂肪组织显示白细胞浸润增加，VAT 中的白细胞浸润高于 SAT，并且涉及巨噬细胞、T 细胞和自然杀伤 (NK) 细胞。缺氧培养调节人脂肪组织 SVF 中炎症细胞因子的分泌和代谢应激反应基因的转录。肥胖参与者的脂肪细胞直径增加，脂肪组织毛细血管密度减少。抑制 c-Jun 末端激酶 (JNK) 或 p38 可显着减弱缺氧诱导的 SVF 炎症反应。缺氧会诱导脂肪组织中 p38 的磷酸化。肥胖的人体脂肪组织的特点是存在特异性炎症细胞浸润，不仅涉及巨噬细胞，还涉及 T 细胞和 NK 细胞。缺氧诱导人体脂肪组织SVF分泌炎症细胞因子，其主要来源是脂肪组织巨噬细胞。这些数据表明p38参与缺氧引起的炎症的调节，并表明脂肪细胞直径和脂肪组织毛细血管密度的改变可能是脂肪组织缺氧的潜在根本原因。
Hypoxia has been implicated as a cause of adipose tissue inflammation in obesity, although the inflammatory response of human adipose tissue to hypoxia is not well understood. The goal of this study was to define in vitro inflammatory responses of human adipose tissue to hypoxia and identify molecular mechanisms of hypoxia-induced inflammation. The inflammatory milieu and responses of visceral (VAT) and subcutaneous (SAT) adipose tissue explants and purified stromovascular cells (SVFs) from obese and lean humans were studied in an in vitro hypoxic culture system using quantitative real-time PCR, ELISA, western blotting, immunofluorescence microscopy, flow cytometry and immunohistochemistry. Human adipose tissue in obesity demonstrates an increased leucocyte infiltrate that is greater in VAT than SAT and involves macrophages, T cells and natural killer (NK) cells. Hypoxic culture regulates inflammatory cytokine secretion and transcription of metabolic stress response genes in human adipose tissue SVF. Adipocyte diameter is increased and adipose tissue capillary density is decreased in obese participants. Inhibition of c-Jun terminal kinase (JNK) or p38 significantly attenuates hypoxia-induced SVF inflammatory responses. Hypoxia induces phosphorylation of p38 in adipose tissue. Human adipose tissue in obesity is characterised by a depot-specific inflammatory cell infiltrate that involves not only macrophages, but also T cells and NK cells. Hypoxia induces inflammatory cytokine secretion by human adipose tissue SVF, the primary source of which is adipose tissue macrophages. These data implicate p38 in the regulation of hypoxia-induced inflammation and suggest that alterations in adipocyte diameter and adipose tissue capillary density may be potential underlying causes of adipose tissue hypoxia.
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影响因子：
4.9
作者：
O'Rourke, R. W.;Metcalf, M. D.;White, A. E.;Madala, A.;Winters, B. R.;Maizlin, I. I.;Jobe, B. A.;Roberts, C. T., Jr.;Slifka, M. K.;Marks, D. L.
通讯作者：
Marks, D. L.
影响因子：
5.8
作者：
Aron-Wisnewsky, Judith;Tordjman, Joan;Clement, Karine
通讯作者：
Clement, Karine
影响因子：
4.8
作者：
Li, Guolian;Barrett, Eugene J.;Liu, Zhenqi
通讯作者：
Liu, Zhenqi
影响因子：
9.8
作者：
Fain, John N.;Buehrer, Ben;Madan, Atul K.
通讯作者：
Madan, Atul K.
影响因子：
8.8
作者：
Kabon, B;Nagele, A;Kurz, A
通讯作者：
Kurz, A