IL-6 regulates adipose deposition and homeostasis in lymphedema
IL-6 regulates adipose deposition and homeostasis in lymphedema
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DOI：
10.1152/ajpheart.01019.2013
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发表时间：
2014-05-01
影响因子：
4.8
通讯作者：
Mehrara, Babak J.
中科院分区：
文献类型：
--
作者：
Cuzzone, Daniel A.;Weitman, Evan S.;Mehrara, Babak J.
淋巴水肿（LE）是一种以慢性肢体肿胀和脂肪沉积为特征的疾病。虽然淋巴损伤是这种病理学所必需的，但引起水肿的机制仍不清楚。IL-6是肥胖症中脂肪稳态的已知调节剂，并且已显示在原发性和继发性水肿模型中增加。因此，本研究的目的是确定IL-6在水肿脂肪沉积中的作用。IL-6的表达进行了分析，在临床组织标本和血清患者或没有LE，以及在两个小鼠模型的淋巴损伤。此外，我们分析了CD 4（+）细胞（CD 4KO）或IL-6表达（IL-6 KO）缺陷小鼠或用IL-6或CD 4耗竭抗体的小分子抑制剂治疗的小鼠中的IL-6表达/脂肪沉积，以确定IL-6表达如何调节以及IL-6表达变化对淋巴损伤后脂肪沉积的影响。LE患者和接受尾部淋巴切除治疗的小鼠的组织和血清中IL-6及其下游介质的表达显著升高。IL-6的表达与脂肪沉积和CD 4（+）炎症相关，并且在CD 4KO小鼠中显著降低。IL-6功能的丧失导致尾淋巴损伤后脂肪沉积显著增加。我们的研究结果表明，IL-6是增加的结果脂肪沉积和CD 4（+）细胞炎症水肿。此外，我们的研究表明，IL-6在水肿中的表达起到限制脂肪积累的作用。
Lymphedema (LE) is a morbid disease characterized by chronic limb swelling and adipose deposition. Although it is clear that lymphatic injury is necessary for this pathology, the mechanisms that underlie lymphedema remain unknown. IL-6 is a known regulator of adipose homeostasis in obesity and has been shown to be increased in primary and secondary models of lymphedema. Therefore, the purpose of this study was to determine the role of IL-6 in adipose deposition in lymphedema. The expression of IL-6 was analyzed in clinical tissue specimens and serum from patients with or without LE, as well as in two mouse models of lymphatic injury. In addition, we analyzed IL-6 expression/adipose deposition in mice deficient in CD4(+) cells (CD4KO) or IL-6 expression (IL-6KO) or mice treated with a small molecule inhibitor of IL-6 or CD4 depleting antibodies to determine how IL-6 expression is regulated and the effect of changes in IL-6 expression on adipose deposition after lymphatic injury. Patients with LE and mice treated with lymphatic excision of the tail had significantly elevated tissue and serum expression of IL-6 and its downstream mediator. The expression of IL-6 was associated with adipose deposition and CD4(+) inflammation and was markedly decreased in CD4KO mice. Loss of IL-6 function resulted in significantly increased adipose deposition after tail lymphatic injury. Our findings suggest that IL-6 is increased as a result of adipose deposition and CD4(+) cell inflammation in lymphedema. In addition, our study suggests that IL-6 expression in lymphedema acts to limit adipose accumulation.