PLAG (1-Palmitoyl-2-Linoleoyl-3-Acetyl-rac-Glycerol) Modulates Eosinophil Chemotaxis by Regulating CCL26 Expression from Epithelial Cells.
PLAG (1-Palmitoyl-2-Linoleoyl-3-Acetyl-rac-Glycerol) Modulates Eosinophil Chemotaxis by Regulating CCL26 Expression from Epithelial Cells.
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DOI：
10.1371/journal.pone.0151758
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Kim JW
中科院分区：
文献类型：
--
作者：
Jeong J;Kim YJ;Yoon SY;Kim YJ;Kim JH;Sohn KY;Kim HJ;Han YH;Chong S;Kim JW
循环和痰中嗜酸性粒细胞数量的增加与哮喘的严重程度有关。呼吸道上皮细胞产生趋化因子(C-C基序)配体(CCL)，募集和激活嗜酸性粒细胞。(1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol)是一种化学合成的单乙酰二甘油酯，是梅花鹿鹿角的主要成分，已被用于东方医学。本研究旨在探讨雷公藤多糖缓解哮喘表型的分子机制。用白介素4(IL-4)刺激人肺泡基底上皮细胞A549和角质形成细胞HaCaT，RT-PCR检测趋化因子的表达。白介素4诱导的基因表达受白介素G共同作用的影响。经酶联免疫吸附试验证实，Plag可显著阻断刺激的上皮细胞CCL26的表达。由IL-4介导的磷酸化和核转位激活的信号转导和转录激活子6(STAT6)的转录活性被Plag浓度依赖性地下调。在卵白蛋白诱导的小鼠模型中，给予Plag可减少免疫细胞向呼吸道的渗透。对分离的支气管肺泡灌洗液(BALF)细胞的细胞学分析表明，Plag可明显减少嗜酸性粒细胞的渗入。此外，Plag还能抑制A549诱导的小鼠骨髓来源的嗜酸性粒细胞和人嗜酸性粒细胞株EoL-1的迁移。
Increased number of eosinophils in the circulation and sputum is associated with the severity of asthma. The respiratory epithelium produces chemokine (C-C motif) ligands (CCL) which recruits and activates eosinophils. A chemically synthesized monoacetyl-diglyceride, PLAG (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol) is a major constituent in the antlers of Sika deer (Cervus nippon Temminck) which has been used in oriental medicine. This study was aimed to investigate the molecular mechanism of PLAG effect on the alleviation of asthma phenotypes. A549, a human alveolar basal epithelial cell, and HaCaT, a human keratinocyte, were activated by the treatment of interleukin-4 (IL-4), and the expression of chemokines, known to be effective on the induction of eosinophil migration was analyzed by RT-PCR. The expression of IL-4 induced genes was modulated by the co-treatment of PLAG. Especially, CCL26 expression from the stimulated epithelial cells was significantly blocked by PLAG, which was confirmed by ELISA. The transcriptional activity of signal transducer and activator of transcription 6 (STAT6), activated by IL-4 mediated phosphorylation and nuclear translocation, was down-regulated by PLAG in a concentration-dependent manner. In ovalbumin-induced mouse model, the infiltration of immune cells into the respiratory tract was decreased by PLAG administration. Cytological analysis of the isolated bronchoalveolar lavage fluid (BALF) cells proved the infiltration of eosinophils was significantly reduced by PLAG. In addition, PLAG inhibited the migration of murine bone marrow-derived eosinophils, and human eosinophil cell line, EoL-1, which was induced by the addition of A549 culture medium.