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  • Title: The JNk/NFkappaB pathway is required to activate murine lymphocytes induced by a sulfated polysaccharide from Ecklonia cava.
    Author: Ahn G, Bing SJ, Kang SM, Lee WW, Lee SH, Matsuda H, Tanaka A, Cho IH, Jeon YJ, Jee Y.
    Journal: Biochim Biophys Acta; 2013 Mar; 1830(3):2820-9. PubMed ID: 23262141.
    Abstract:
    BACKGROUND: The proven immunomodulatory and immune system activating properties of Ecklonia cava (E. cava) have been attributed to its plentiful polysaccharide content. Therefore, we investigated whether the sulfated polysaccharide (SP) of E. cava specifically activates the protein kinases (MAPKs) and nuclear factor-kappaB (NFkappaB) to incite immune responses. METHODS: To assess immune responsiveness, lymphocytes were isolated from spleens of ICR mice and cultured with SP and its inhibitors. Assays included 3H-thymidine incorporation, flow cytometry, real time polymerase chain reaction (rtPCR), enzyme linked immunosorbent assay (ELISA), intracellular cytokine assay. Western blot, and electrophoretic mobility shift assay (EMSA). RESULTS: SP dose-dependently increased the proliferation of lymphocytes without cytotoxicity. In particular, SP markedly enhanced the proliferation and differentiation of CD3+ mature T cells and CD45R/B220+ pan B cells. Additionally, SP increased the expression and/or production of IL-2, IgG(1a), and IgG(2b) compared to that in untreated cells. The subsequent application of JNK (SP600125), NFkappaB (PDTC), and serine protease (TPCK) inhibitors significantly inhibited the proliferation and IL-2 production of SP-treated lymphocytes as well as the phosphorylation of JNK and IkappaB, the activation of nuclear NFkappaB p65, and binding of NFkappaB p65 DNA. Moreover, co-application of both JNK and NFkappaB inhibitors completely blocked the proliferation of lymphocytes even in the presence of SP. CONCLUSION: These results suggest that SP induced T and B cell responses via both JNK and NFkappaB pathways. GENERAL SIGNIFICANCE: The effect of SP on splenic lymphocyte activation was assayed here for the first time and indicated the underlying functional mechanism.
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