title: Zymosan and PMA activate the immune responses of Mutz3-derived dendritic cells synergistically.
abstract: Beta-glucan (β-glucan) including zymosan has been known as a super food because of its multifunctional activities, such as the enhancement of immune responses. To study the functional mechanism of β-glucan in immune stimulation, the effect of zymosan on dendritic cell (DC) was investigated by monitoring the production of TNF-α, a pro-inflammatory cytokine. DC was differentiated from Mutz-3, a human acute myeloid leukemia cell line, by cytokine treatment and characterized. DC-specific cell surface markers were increased during the differentiation. Especially, Dectin-1, a β-glucan receptor, was upregulated during DC differentiation, and mediated zymosan-induced TNF-α production, which was inhibited by silencing of dectin-1. Zymosan exhibited synergistic effect with other immune stimuli such as lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMA), a well-known PKC activator. Simultaneous treatment of zymosan and PMA enhanced the nuclear translocation of NF-κB subunits, p50 and p65, mediating the increase of TNF-α production. Bay 11-7082, an NF-κB inhibitor, blocked morphological changes and TNF-α production induced by zymosan and/or PMA treatment. Western blot analysis has showed zymosan-Dectin-1 pathway mediated destructive phosphorylation of inhibitor of NF-κB (IκB) kinase α subunit (IKKα) in IKK complexes, while PMA-PKC pathway regulated selective phosphorylation and degradation of IKKβ. Simultaneous phosphorylation of separate IKK subunits by co-treatment of zymosan and PMA resulted in cooperative activation of NF-κB and TNF-α production.
authors.affiliation: Biomedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Republic of Korea.
authors.forename: Jae Sung
authors.initials: JS
authors.lastname: Song
authors.affiliation: Biomedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Republic of Korea.
authors.forename: Young-Jun
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Han Nam University, Daejeon 306-791, Republic of Korea.
authors.forename: Kyu Ung
authors.initials: KU
authors.lastname: Han
authors.affiliation: Bioindustrial Process Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 580-185, Republic of Korea.
authors.forename: Byung Dae
authors.initials: BD
authors.lastname: Yoon
authors.affiliation: Biomedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Republic of Korea. Electronic address: wjkim@kribb.re.kr.
authors.forename: Jae Wha
authors.initials: JW
authors.lastname: Kim
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D008954:Models, Biological; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010641:Phenotype; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015054:Zymosan / Q000494:pharmacology*
chemical_list: D015703:Antigens, CD; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D015054:Zymosan; D013755:Tetradecanoylphorbol Acetate
keywords: IKKα; IKKβ; NF-κB; PMA; TNF-α; Zymosan