Else Kröner-Fresenius-Centre for Nutritional Medicine, Freising, Germany.
Am J Physiol Endocrinol Metab. 2011 Feb;300(2):E304-11. doi: 10.1152/ajpendo.00143.2010. Epub 2010 Nov 9.
Infiltration of immune cells into adipose tissue plays a central role in the pathophysiology of obesity-associated low-grade inflammation. The aim of this study was to analyze the role of adipocyte NF-κB signaling in the regulation of the chemokine/adipokine interferon-γ-induced protein 10 kDa (IP-10) and adipocyte-mediated T cell migration. Therefore, the regulation of IP-10 was investigated in adipose tissue of male C57BL/6J mice, primary human and 3T3-L1 preadipocytes/adipocytes. To specifically block the NF-κB pathway, 3T3-L1 cells stably overexpressing a transdominant mutant of IκBα were generated, and the chemical NF-κB inhibitor Bay117082 was used. Adipocyte-mediated T cell migration was assessed by a migration assay. It could be shown that IP-10 expression was higher in mature adipocytes compared with preadipocytes. Induced IP-10 expression and secretion were completely blocked by an NF-κB inhibitor in 3T3-L1 and primary human adipocytes. Stable overexpression of a transdominant mutant of IκBα in 3T3-L1 adipocytes led to an inhibition of basal and stimulated IP-10 expression and secretion. T cell migration was induced by 3T3-L1 adipocyte-conditioned medium, and both basal and induced T cell migration was strongly inhibited by stable overexpression of a transdominant IκBα mutant. In addition, with the use of an anti-IP-10 antibody, a significant decrease of adipocyte-induced T cell migration was shown. In conclusion, in this study, we could demonstrate that the NF-κB pathway is essential for the regulation of IP-10 in 3T3-L1 and primary human adipocytes. Adipocytes rather than preadipocytes contribute to NF-κB-dependent IP-10 expression and secretion. Furthermore, NF-κB-dependent factors and especially IP-10 represent novel signals from adipocytes to induce T cell migration.
免疫细胞浸润脂肪组织在肥胖相关低度炎症的病理生理学中起着核心作用。本研究旨在分析脂肪细胞 NF-κB 信号在调节趋化因子/脂肪因子干扰素-γ诱导蛋白 10 kDa（IP-10）和脂肪细胞介导的 T 细胞迁移中的作用。因此，研究人员分析了雄性 C57BL/6J 小鼠、原代人及 3T3-L1 前体脂肪细胞/脂肪细胞的脂肪组织中 IP-10 的调节。为了特异性阻断 NF-κB 通路，研究人员生成了稳定过表达 IκBα 反式显性突变体的 3T3-L1 细胞，并使用化学 NF-κB 抑制剂 Bay117082。通过迁移实验评估脂肪细胞介导的 T 细胞迁移。结果表明，与前体脂肪细胞相比，成熟脂肪细胞中 IP-10 的表达更高。在 3T3-L1 和原代人脂肪细胞中，NF-κB 抑制剂完全阻断了 IP-10 的诱导表达和分泌。3T3-L1 脂肪细胞中稳定过表达反式显性 IκBα 突变体导致基础和刺激诱导的 IP-10 表达和分泌受到抑制。3T3-L1 脂肪细胞条件培养基诱导 T 细胞迁移，稳定过表达反式显性 IκBα 突变体强烈抑制基础和诱导的 T 细胞迁移。此外，使用抗 IP-10 抗体可显著降低脂肪细胞诱导的 T 细胞迁移。综上所述，在这项研究中，研究人员证明了 NF-κB 通路对于 3T3-L1 和原代人脂肪细胞中 IP-10 的调节至关重要。脂肪细胞而非前体脂肪细胞参与 NF-κB 依赖性 IP-10 表达和分泌。此外，NF-κB 依赖性因子，特别是 IP-10，代表了脂肪细胞诱导 T 细胞迁移的新信号。
