title: The immunomodulatory activities of pullulan and its derivatives in human pDC-like CAL-1 cell line.
abstract: In this study, acidic and alkaline pullulan derivates were synthesized and their immunomodulatory activities compared to pullulan were investigated in human pDC-like CAL-1 cell line. Pullulan was reacted respectively with succinic anhydride and N-(-2-aminoethyl)-1,3-propanediamine/N,N-carbonyl diimidazole to form acidic pullulan monosuccinate (SUPL) and alkaline pullulan-g-N-(-2-aminoethyl)-1,3-propanediamine (AMPL). In CAL-1 cells, pullulan, SUPL and AMPL up-regulated the mRNA expressions of type I interferons (IFN), including IFN-α and IFN-β1, and some other proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-23 (IL-23), and also significantly enhanced the protein expressions of IFN-α and TNF-α. The activation of nuclear factor kappa B (NF-κB) and the nuclear translocations of interferon regulation factors (IRFs), including IRF-3 and IRF-5, exhibited pivotal roles in the immune responses induced by pullulan, SUPL and AMPL. By comparison, pullulan and SUPL displayed weak effects on the activation of CAL-1 cells, but AMPL showed remarkably enhanced immunomodulatory activities, which were comparable to that induced by R848, an agonist for Toll-like receptor (TLR) 7/8. Our results suggested that AMPL, as an alkaline pullulan derivative, could be used as a potent immunomodulatory agent in the food and pharmacological fields.
authors: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Huanhuxi Road, Hexi District, Tianjin 300060, PR China; Research Center of Basic Medical Science & School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, PR China.
authors: Fang
authors: F
authors: Wang
authors: Research Center of Basic Medical Science & School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, PR China.
authors: Linan
authors: L
authors: Qiao
authors: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Huanhuxi Road, Hexi District, Tianjin 300060, PR China.
authors: Liwei
authors: L
authors: Chen
authors: Research Center of Basic Medical Science & School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, PR China.
authors: Cong
authors: C
authors: Zhang
authors: Research Center of Basic Medical Science & School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, PR China.
authors: Yan
authors: Y
authors: Wang
authors: Research Center of Basic Medical Science & School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, PR China.
authors: Yinsong
authors: Y
authors: Wang
authors: Research Center of Basic Medical Science & School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, PR China. Electronic address: liuyuanyuan01@tmu.edu.cn.
authors: Yuanyuan
authors: Y
authors: Liu
authors: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Huanhuxi Road, Hexi District, Tianjin 300060, PR China; Research Center of Basic Medical Science & School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, PR China. Electronic address: zhangning@tmu.edu.cn.
authors: Ning
authors: N
authors: Zhang
mesh_terms: D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D005936:Glucans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007155:Immunologic Factors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D005936:Glucans; D007155:Immunologic Factors; D016898:Interferon-alpha; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta; C009109:pullulan
keywords: Derivative; Human pDC-like CAL-1 cell line; Immunomodulatory; Pullulan