The lipopolysaccharide-activated toll-like receptor (TLR)-4 induces synthesis of the closely related receptor TLR-2 in adipocytes
The lipopolysaccharide-activated toll-like receptor (TLR)-4 induces synthesis of the closely related receptor TLR-2 in adipocytes
复制标题
DOI：
10.1074/jbc.m002137200
复制
发表时间：
2000-08-11
影响因子：
4.8
通讯作者：
Scherer, PE
中科院分区：
文献类型：
--
作者：
Lin, Y;Lee, H;Scherer, PE
脂肪细胞在全身能量平衡中的中心调节作用已经得到了很好的确立，然而，最近的研究结果表明，前脂肪细胞和脂肪细胞可能在先天性和适应性免疫反应的调节中发挥重要的生理作用。为了系统地表征介导病原体识别的脂肪细胞的分子机制，我们将我们的分析集中在最近发现的Toll样受体（TLR）上。这些受体被认为是细胞对细菌脂多糖（LPS）反应的介质。在这里，我们报道了从3 T3-L1脂肪细胞中克隆的小鼠TLR-2的功能特性，TLR-2的合成在脂肪细胞中被LPS、TNF α和酵母细胞壁提取物酵母聚糖强烈诱导，TLR-2经历漫长的细胞内成熟过程，从ER排出的半衰期约为3小时。此外，脂多糖处理脂肪细胞导致基因表达水平的显著变化，包括合成一组不同的分泌蛋白，如白细胞介素-6。我们的研究表明，在脂肪细胞中存在完全完整的先天免疫途径，该途径可被与细胞表面结合的LPS激活，并导致免疫调节分子的分泌。
The central regulatory role of the adipocyte in whole body energy homeostasis is well established, However, recent findings suggest that preadipocytes and adipocytes may play an important physiological role in the regulation of both the innate and adaptive immune response. To systematically characterize the molecular machinery of the adipocyte that mediates the recognition of pathogens, we have focused our analysis on the recently identified Toll-like receptors (TLRs). These receptors have been implicated as mediators of the cellular response to bacterial lipopolysacharides (LPSs), Here, we report the cloning and functional characterization of mouse TLR-2 from 3T3-L1 adipocytes, TLR-2 synthesis is strongly induced in the adipocyte by LPS, TNF alpha, and the yeast cell wall extract zymosan, TLR-2 undergoes a lengthy intracellular maturation process with a half-life of exit from the ER of approximately 3 h, Furthermore, LPS treatment of adipocytes results in dramatic changes at the level of gene expression, including the synthesis of a distinct set of secretory proteins such as interleukin-6, Our studies demonstrate the presence of a fully intact pathway of innate immunity in the adipocyte that can be activated by LPS binding to the cell surface and results in the secretion of immunomodulatory molecules.