Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 974, Taiwan.
Mar Drugs. 2013 Apr 22;11(4):1336-50. doi: 10.3390/md11041336.
Dendritic cells (DCs) are antigen presenting cells, which can present antigens to T-cells and play an important role in linking innate and adaptive immunity. DC maturation can be induced by many stimuli, including pro-inflammatory cytokines and bacterial products, such as lipopolysaccharides (LPS). Here, we examined the immunomodulatory effects of marine cembrane compounds, (9E,13E)-5-acetoxy-6-hydroxy-9,13-dimethyl-3- methylene-3,3a,4,5,6,7,8,11,12,14a-decahydro-2H-cyclotrideca[b]furan-2-one (1), (9E,13E)- 5-acetoxy-6-acetyl-9,13-dimethyl-3-methylene-3,3a,4,5,6,7,8,11,12,14a-decahydro-2H-cyclotrideca[b]furan-2-one (2), lobocrassin B (3), (-)14-deoxycrassin (4), cembranolide B (5) and 13-acetoxysarcocrassolide (6) isolated from a soft coral, Lobophytum crassum, on mouse bone marrow-derived dendritic cells (BMDCs). The results revealed that cembrane-type diterpenoids, especially lobocrassin B, effectively inhibited LPS-induced BMDC activation by inhibiting the production of TNF-α. Pre-treatment of BMDCs with Lobocrassin B for 1 h is essential to prohibit the following activation induced by various toll-like receptor (TLR) agonists, such as LPS, zymosan, lipoteichoic acid (LTA) and Pam2CSK4. Inhibition of NF-κB nuclear translocation by lobocrassin B, which is a key transcription factor for cytokine production in TLR signaling, was evident as assayed by high-content image analysis. Lobocrassin B attenuated DC maturation and endocytosis as the expression levels of MHC class II and the co-stimulatory molecules were downregulated, which may affect the function of DCs to initiate the T-cell responses. Thus, lobocrassin B may have the potential in treatment of immune dysregulated diseases in the future.
树突状细胞 (DCs) 是抗原呈递细胞，可将抗原呈递给 T 细胞，并在连接先天免疫和适应性免疫方面发挥重要作用。DC 的成熟可被许多刺激诱导，包括促炎细胞因子和细菌产物，如脂多糖 (LPS)。在这里，我们研究了海洋枞烷类化合物的免疫调节作用，(9E,13E)-5-乙酰氧基-6-羟基-9,13-二甲基-3-亚甲基-3,3a,4,5,6,7,8,11,12,14a-十氢-2H-环十三[b]呋喃-2-酮 (1)、(9E,13E)-5-乙酰氧基-6-乙酰基-9,13-二甲基-3-亚甲基-3,3a,4,5,6,7,8,11,12,14a-十氢-2H-环十三[b]呋喃-2-酮 (2)、洛伯辛 B (3)、(-)14-脱氧克拉辛 (4)、枞醇 B (5) 和 13-乙酰氧基沙罗醇 (6) 对从小软珊瑚 Lobophytum crassum 中分离出的骨髓来源的树突状细胞 (BMDC) 的影响。结果表明，枞烷型二萜类化合物，特别是洛伯辛 B，通过抑制 TNF-α 的产生，有效抑制 LPS 诱导的 BMDC 激活。用洛伯辛 B 预处理 BMDC 1 h 对于抑制各种 Toll 样受体 (TLR) 激动剂，如 LPS、酵母聚糖、脂磷壁酸 (LTA) 和 Pam2CSK4 引起的后续激活是必不可少的。通过高内涵图像分析检测到，洛伯辛 B 抑制 NF-κB 核易位，NF-κB 是 TLR 信号中细胞因子产生的关键转录因子。洛伯辛 B 下调 MHC Ⅱ类和共刺激分子的表达水平，从而减弱 DC 成熟和内吞作用，这可能影响 DC 启动 T 细胞反应的功能。因此，洛伯辛 B 未来可能具有治疗免疫失调性疾病的潜力。
