Regulation of inflammatory response of macrophages and induction of regulatory T cells by using retinoic acid-loaded nanostructured lipid carrier
Regulation of inflammatory response of macrophages and induction of regulatory T cells by using retinoic acid-loaded nanostructured lipid carrier
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DOI：
10.1080/09205063.2018.1493671
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发表时间：
2019-01
期刊：
影响因子：
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通讯作者：
Khadijah Zai;Narumi Ishihara;Hiroyuki Oguchi;Masato Hirota;A. Kishimura;Takeshi Mori;K. Hase;Y. Katayama
中科院分区：
文献类型：
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作者：
Khadijah Zai;Narumi Ishihara;Hiroyuki Oguchi;Masato Hirota;A. Kishimura;Takeshi Mori;K. Hase;Y. Katayama
摘要全反式维甲酸(ATRA)的免疫调节作用在自身免疫性疾病的治疗中备受关注。全反式维甲酸是一种化学不稳定的分子，需要适当的制剂才能靶向传递。在这里，我们研究了用于ATRA配方的纳米结构脂质载体(NLC)。NLC是一种具有代表性的纳米制剂，特别适合于口服给药。建立了全反式维甲酸NLC(NLC-RA)的制备工艺，使ATRA在制备过程中的降解降至最低。由此获得的NLC-RA可被巨噬细胞摄取，并通过抑制NF-κB信号和促进抗炎细胞因子的产生而诱导抗炎反应。此外，在与树突状细胞共培养系统中，NLC-RA促进了原始T细胞向调节性T细胞的分化。这些结果表明，NLC-RA是治疗自身免疫性疾病，特别是肠道疾病的一种有前途的替代疗法。
Abstract Immunomodulatory function of all-trans retinoic acid (ATRA) has been gathering much attention for the therapy of autoimmune diseases. ATRA is a chemically unstable molecule which requires proper formulation for targeted delivery. Here we examined nanostructured lipid carrier (NLC) for the formulation of ATRA. NLC is a representative nanoparticle formulation especially suited for oral delivery. We established the preparation procedures of ATRA-containing NLC (NLC-RA) which minimizes the degradation of ATRA during the preparation process. NLC-RA thus obtained was taken up by macrophages and induced anti-inflammatory response via suppressing NF-κB signaling as well as via enhancing the production of anti-inflammatory cytokines. Moreover, NLC-RA enhanced differentiation of naïve T cells to regulatory T cells in the co-culture system with dendritic cells. These results suggest that NLC-RA is a promising alternative therapy for the autoimmune diseases especially intestinal bowel disease.