IL‐1 directly inhibits milk lipid production in lactating mammary epithelial cells concurrently with enlargement of cytoplasmic lipid droplets
IL‐1 directly inhibits milk lipid production in lactating mammary epithelial cells concurrently with enlargement of cytoplasmic lipid droplets
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DOI：
10.1016/j.yexcr.2018.06.038
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发表时间：
2018-09
影响因子：
3.7
通讯作者：
Kota Matsunaga;Yusaku Tsugami;Aogu Kumai;Takahiro Suzuki;T. Nishimura;Ken Kobayashi
中科院分区：
文献类型：
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作者：
Kota Matsunaga;Yusaku Tsugami;Aogu Kumai;Takahiro Suzuki;T. Nishimura;Ken Kobayashi
哺乳期乳腺中的乳腺上皮细胞（MEC）产生乳脂，为婴儿的适当生长提供大部分热量和生物活性脂质。然而，在乳腺炎乳腺中，分泌的乳汁脂质通常减少，同时IL-1β、IL-6和TNF-α增加。在这项研究中，我们研究了这些细胞因子是否直接影响脂质的产生和分泌。采用油酸培养法建立了具有高脂分泌能力的哺乳期MEC培养模型。TNF-α、IL-1β和IL-6对泌乳期MEC脂质产生和分泌的影响不同。特别是，与对照组相比，IL-1β处理显著降低了分泌的甘油三酯的量97%，同时MEC中细胞质脂滴增大。IL-1β还降低了牛奶脂质产生途径中Fabp 3和Srebp 1的mRNA表达以及水通道蛋白3、GLUT-1和亲脂蛋白的量。此外，IL-1β可使STAT 5和糖皮质激素信号失活以诱导MEC产奶，而STAT 3和NFκB信号被激活。IL-1β诱导MEC表达IL-6和TNF-α。因此，我们认为IL-1β是哺乳期MEC中脂质产生和分泌的关键抑制剂。
Mammary epithelial cells (MECs) in lactating mammary glands produce milk lipid, which provides a large percentage of calories and bioactive lipids for appropriate infant growth. However, secreted milk lipid is often reduced concurrently with increases in IL-1β, IL-6, and TNF-α in mammary glands with mastitis. In this study, we investigated whether those cytokines directly influenced lipid production and secretion. A lactating MEC culture model with high lipid production ability was prepared by culture with oleic acid. TNF-α, IL-1β, and IL-6 differentially affected lipid production and secretion in lactating MECs. In particular, IL-1β treatment significantly reduced amounts of secreted triglycerides by 97% compared with the control concurrently with enlargement of cytoplasmic lipid droplets in MECs. IL-1β also decreased mRNA expression ofFabp3andSrebp1and the amount of aquaporin 3, GLUT-1 and adipophilin in the milk lipid production pathway. Furthermore, IL-1β inactivated STAT5 and glucocorticoid signaling to induce milk production in MECs, whereas STAT3 and NFκB signaling was activated. IL-1β induced mRNA expression of IL-6 and TNF-α in MECs. Therefore, we suggest that IL-1β is a key inhibitor of lipid production and secretion in lactating MECs.