title: Dectin-1-mediated signaling leads to characteristic gene expressions and cytokine secretion via spleen tyrosine kinase (Syk) in rat mast cells.
abstract: Dectin-1 recognizes β-glucan and plays important roles for the antifungal immunity through the activation of spleen tyrosine kinase (Syk) in dendritic cells or macrophages. Recently, expression of Dectin-1 was also identified in human and mouse mast cells, although its physiological roles were largely unknown. In this report, rat mast cell line RBL-2H3 was analyzed to investigate the molecular mechanism of Dectin-1-mediated activation and responses of mast cells. Treatment of cells with Dectin-1-specific agonist curdlan induced tyrosine phosphorylation of cellular proteins and the interaction of Dectin-1 with the Src homology 2 domain of Syk. These responses depended on tyrosine phosphorylation of the hemi-immunoreceptor tyrosine-based activation motif in the cytoplasmic tail of Dectin-1, whereas they were independent of the γ-subunit of high-affinity IgE receptor. DNA microarray and real-time PCR analyses showed that Dectin-1-mediated signaling stimulated gene expression of transcription factor Nfkbiz and inflammatory cytokines, such as monocyte chemoattractant protein-1, IL-3, IL-4, IL-13, and tumor necrosis factor (TNF)-α. The response was abrogated by pretreatment with Syk inhibitor R406. These results suggest that Syk is critical for Dectin-1-mediated activation of mast cells, although the signaling differs from that triggered by FcϵRI activation. In addition, these gene expressions induced by curdlan stimulation were specifically observed in mast cells, suggesting that Dectin-1-mediated signaling of mast cells offers new insight into the antifungal immunity.
authors.affiliation: From the Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and Locomotor Medicine, the Division of Genome Science and Microbiology, Department of Pathological Sciences, and.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: the Division of Genome Science and Microbiology, Department of Pathological Sciences, and the Organization for Life Science Advancement Programs, University of Fukui, Fukui 910-1193, Japan.
authors.forename: Kazuyasu
authors.initials: K
authors.lastname: Chihara
authors.affiliation: the Division of Genome Science and Microbiology, Department of Pathological Sciences, and the Third Department of Internal Medicine, Faculty of Medical Sciences, and.
authors.forename: Chisato
authors.initials: C
authors.lastname: Honjoh
authors.affiliation: the Division of Genome Science and Microbiology, Department of Pathological Sciences, and the Organization for Life Science Advancement Programs, University of Fukui, Fukui 910-1193, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Takeuchi
authors.affiliation: the Division of Genome Science and Microbiology, Department of Pathological Sciences, and the Organization for Life Science Advancement Programs, University of Fukui, Fukui 910-1193, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Yamauchi
authors.affiliation: the Division of Genome Science and Microbiology, Department of Pathological Sciences, and.
authors.forename: Hatsumi
authors.initials: H
authors.lastname: Yoshiki
authors.affiliation: From the Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and Locomotor Medicine.
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Fujieda
authors.affiliation: the Division of Genome Science and Microbiology, Department of Pathological Sciences, and the Organization for Life Science Advancement Programs, University of Fukui, Fukui 910-1193, Japan ksada@u-fukui.ac.jp.
authors.forename: Kiyonao
authors.initials: K
authors.lastname: Sada
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism / Q000382:microbiology; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D007113:Immunity, Innate; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D008407:Mast Cells / Q000166:cytology / Q000201:enzymology*; D051379:Mice; D009181:Mycoses / Q000276:immunology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D000072377:Syk Kinase; D014443:Tyrosine / Q000737:chemistry; D047071:beta-Glucans / Q000737:chemistry / Q000378:metabolism; D000099181:Dectin-1
chemical_list: D000935:Antifungal Agents; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; D014443:Tyrosine; D047071:beta-Glucans; D000099181:Dectin-1; C038459:curdlan; C000606896:SYK protein, human; C000606897:Syk protein, mouse; C000606898:Syk protein, rat
keywords: Dectin-1; Fungi; Host Defense; Innate Immunity; Mast Cell; Phosphotyrosine Signaling; Signal Transduction; Syk