title: Immunomodulatory effect of marine cembrane-type diterpenoids on dendritic cells.
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.
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 974, Taiwan. jouyuan22@gmail.com
authors.forename: Ching-Yen
authors.initials: CY
authors.lastname: Lin
authors.forename: Mei-Chin
authors.initials: MC
authors.lastname: Lu
authors.forename: Jui-Hsin
authors.initials: JH
authors.lastname: Su
authors.forename: Ching-Liang
authors.initials: CL
authors.lastname: Chu
authors.forename: David
authors.initials: D
authors.lastname: Shiuan
authors.forename: Ching-Feng
authors.initials: CF
authors.lastname: Weng
authors.forename: Ping-Jyun
authors.initials: PJ
authors.lastname: Sung
authors.forename: Kao-Jean
authors.initials: KJ
authors.lastname: Huang
mesh_terms: D000818:Animals; D037421:Anthozoa / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D004705:Endocytosis / Q000187:drug effects; D007155:Immunologic Factors / Q000302:isolation & purification / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D051193:Toll-Like Receptors / Q000819:agonists / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D004224:Diterpenes; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; C585609:lobocrassin B