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首页> 外文期刊>Cytokine >Role of progranulin in adipose tissue innate immunity
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Role of progranulin in adipose tissue innate immunity

机译：Progranulin在脂肪组织先天免疫的作用

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摘要

Regulation of progranulin in adipocytes and its role in inflammation is poorly understood. Aim: (i) to investigate regulation of progranulin in adipocyte differentiation and adipose tissue compartments, (ii) to address progranulin expression in two murine (C57BL/6) models of inflammation. Results: Progranulin expression was induced during adipocyte differentiation. Neither estradiol nor testosterone or metabolic stimuli such as glucose and insulin modified progranulin synthesis. Fatty acids, bile acids and incretins GLP-1 and GIP-1 exerted potent and differential effects on progranulin secretion. LPS, TNF and IL6 significantly increased progranulin secretion. TLR9 agonists decreased and TLR1/2, TLR3, TLR5, and TLR2/6 ligands increased progranulin expression. TLR3-mediated progranulin induction was abrogated by inhibitors of NF-kappa B and PI3K pathways. Progranulin expression between murine epididymal and subcutaneous adipose tissue did not differ in total adipose tissue, in isolated adipocytes or in the stromal-vascular cell fraction (SVC). However, SVC expressed significantly higher levels of progranulin than adipocytes at all sites. In adipocytes, female mice had significantly higher progranulin expression at all sites. An intra-peritoneal LPS challenge in mice did not affect adipose tissue progranulin expression, whereas peritoneal infection by S. aureus increased progranulin expression after 24 h. Conclusions: There are relevant sex-, site- and cell-specific effects on progranulin gene expression that is induced during adipocyte differentiation and modulated by various inflammatory and metabolic factors. Most importantly, ligands for TLR1/2 and TLR2/6 (recognizing S. aureus) in vitro and infection by S. aureus in vivo induce progranulin expression suggesting a role of adipocytes in protection against infection by gram-positive bacteria.
机译：在脂肪细胞中对植物素调节及其在炎症中的作用是较差的理解。目的：（i）调查脂肪细胞分化和脂肪组织隔室中植物蛋白的调节，（ii）在两只鼠（C57bl / 6）炎症模型中地解植物表达。结果：在脂肪细胞分化期间诱导植物蛋白表达。雌二醇和睾酮或代谢刺激都不是葡萄糖和胰岛素修饰的植物合成。脂肪酸，胆汁酸和Incretins GLP-1和GIP-1对Progranulin分泌施加有效和差异影响。 LPS，TNF和IL6显着提高了植物分泌物。 TLR9激动剂减少和TLR1 / 2，TLR3，TLR5和TLR2 / 6配体增加了植物表达。通过NF-κB和PI3K途径的抑制剂废除TLR3介导的植物诱导。鼠相邻和皮下脂肪组织之间的植物胰蛋白表达在分离的脂肪细胞中或在基质血管细胞级分（SVC）中没有不同的脂肪组织。然而，SVC表达了比所有地点的脂肪细胞显着更高水平的植物蛋白。在脂肪细胞中，雌性小鼠在所有地点具有显着高的植物蛋白表达。小鼠腹膜内的LPS挑战不影响脂肪组织植物蛋白表达，而S.Sureus的腹膜感染增加24小时后增加植物表达。结论：在脂肪细胞分化期间诱导和调节各种炎症和代谢因子的植物基因表达有相关的性别，部位和细胞特异性效果。最重要的是，TLR1 / 2和TLR2 / 6（识别S.UUREUS）的配体体外和感染于体内诱导植物表达的体外和感染，表达脂肪细胞在革兰氏阳性细菌的感染保护方面的作用。

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