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Immunomodulatory Effect of Marine Cembrane-Type Diterpenoids on Dendritic Cells
Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 974, Taiwan
Graduate Institute of Marine Biotechnology, National Dong Hwa University, Pingtung 944, Taiwan
Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei 100, Taiwan
* Author to whom correspondence should be addressed.
Received: 26 February 2013; in revised form: 22 March 2013 / Accepted: 27 March 2013 / Published: 22 April 2013
Abstract: 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.
Keywords: antigen presentation; bone-marrow derived dendritic cell (BMDC); marine natural compound; tumor necrosis factor-α
MDPI and ACS Style
Lin, C.-Y.; Lu, M.-C.; Su, J.-H.; Chu, C.-L.; Shiuan, D.; Weng, C.-F.; Sung, P.-J.; Huang, K.-J. Immunomodulatory Effect of Marine Cembrane-Type Diterpenoids on Dendritic Cells. Mar. Drugs 2013, 11, 1336-1350.
Lin C-Y, Lu M-C, Su J-H, Chu C-L, Shiuan D, Weng C-F, Sung P-J, Huang K-J. Immunomodulatory Effect of Marine Cembrane-Type Diterpenoids on Dendritic Cells. Marine Drugs. 2013; 11(4):1336-1350.
Lin, Ching-Yen; Lu, Mei-Chin; Su, Jui-Hsin; Chu, Ching-Liang; Shiuan, David; Weng, Ching-Feng; Sung, Ping-Jyun; Huang, Kao-Jean. 2013. "Immunomodulatory Effect of Marine Cembrane-Type Diterpenoids on Dendritic Cells." Mar. Drugs 11, no. 4: 1336-1350.