Saturated Fatty Acid Increases Lung Macrophages and Augments House Dust Mite-Induced Airway Inflammation in Mice Fed with High-Fat Diet.
Saturated Fatty Acid Increases Lung Macrophages and Augments House Dust Mite-Induced Airway Inflammation in Mice Fed with High-Fat Diet.
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DOI：
10.1007/s10753-017-0550-4
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发表时间：
2017-06
期刊：
影响因子：
5.1
通讯作者：
Sueoka-Aragane N
中科院分区：
文献类型：
--
作者：
Tashiro H;Takahashi K;Sadamatsu H;Kato G;Kurata K;Kimura S;Sueoka-Aragane N
肥胖是严重哮喘的表型之一，被认为是一种异质性综合征;然而，其与气道炎症的相互作用尚未完全了解。本研究的目的是阐明饱和脂肪酸在增强肥胖症患者由屋尘螨（HDM）诱导的气道炎症中的作用。受试者是Balb/c小鼠，喂食高脂饮食（HFD）10周，然后致敏并暴露于HDM。受试者还接受棕榈酸（PA）给药4周，同时致敏和暴露于HDM。通过定量支气管肺泡灌洗（BAL）中炎性细胞的量来评估气道炎症，并测量气道阻力。在体外，脂多糖（LPS）致敏的巨噬细胞由PA刺激。检测培养上清中单核细胞趋化蛋白1（MCP 1）、白细胞介素1β（IL 1β）和肿瘤坏死因子α（TNF α）的含量。与正常食物小鼠相比，HDM致敏和暴露后，HFD小鼠体重显著增加;肺巨噬细胞（包括循环单核细胞和肺泡巨噬细胞）数量增加;支气管肺泡灌洗液（BALF）总细胞计数增加，包括中性粒细胞但不包括嗜酸性粒细胞。在体外，PA诱导MCP-1和增加LPS引发的巨噬细胞IL-1β和TNF-α的产生。在给予PA的HDM小鼠中，与溶媒小鼠相比，BALF总细胞计数增加，包括中性粒细胞，但不包括嗜酸性粒细胞。总之，在HFD小鼠模型中，饱和脂肪酸增加了肺巨噬细胞的数量，并增强了HDM诱导的嗜酸性气道炎症。
Obesity is one of the phenotypes of severe asthma, which is considered to be a heterogeneous syndrome; however, its interaction with airway inflammation is not fully understood. The aim of this study was to clarify the role of saturated fatty acids in augmenting airway inflammation induced by house dust mite (HDM) in obesity. Subjects were Balb/c mice fed a high-fat diet (HFD) for 10 weeks, followed by sensitization and exposure to HDM. Subjects were also administered palmitic acid (PA) for 4 weeks with concurrent sensitization and exposure to HDM. Airway inflammation was assessed by quantifying the amount of inflammatory cells in bronchoalveolar lavage (BAL) and airway resistance was measured. In vitro, lipopolysaccharide (LPS)-primed macrophages were stimulated by PA. The amount of monocyte chemoattractant protein-1 (MCP-1), interleukin-1β (IL-1β), and tumor necrosis factor α (TNF-α) was examined in the supernatant. Compared to normal chow mice, HFD mice underwent significant increases in body weight; increases in number of lung macrophages, including circulating monocytes and alveolar macrophages; and increases in bronchoalveolar lavage fluid (BALF) total cell count, including neutrophils but not eosinophils, after HDM sensitization and exposure. In vitro, PA induced MCP-1 and augmented LPS-primed production of IL-1β and TNF-α in macrophages. Among HDM mice that were administered PA, there was an increase BALF total cell count, including neutrophils but not eosinophils, compared to vehicle mice. In conclusion, saturated fatty acid increased the number of lung macrophages and augmented HDM-induced neutrophilic airway inflammation in a HFD mouse model.