title: Immunomodulation of dendritic cells differentiated in the presence of nicotine with lipopolysaccharide from Porphyromonas gingivalis.
abstract: Tobacco smoking is a significant risk factor for periodontal diseases. Nicotine, one of the most studied constituents in cigarette smoke, is thought to modify immune responses. Dendritic cells (DCs), which are key mediators between innate and adaptive immunity, stimulate naive T cells to differentiate to effector T-cell subsets that may be actively involved in the immunopathogenesis of periodontal diseases. In this study, we evaluated the effects of nicotine and lipopolysaccharide (LPS) from Porphyromonas gingivalis, alone and in combination, on the functions of human monocyte-derived DCs to elucidate the mechanism of tissue destruction of smoking-associated periodontal diseases. P. gingivalis LPS-stimulated DCs differentiated with nicotine (NiDCs) induced lower T-cell proliferation and human leukocyte antigen (HLA)-DR expression, but elevated expression of programmed cell death ligand 1. Additionally, NiDCs impaired interferon-γ production but maintained interleukin (IL)-5 and IL-10 production in co-cultured T cells. Furthermore, NiDCs produced lower levels of proinflammatory cytokines compared with DCs differentiated in the absence of nicotine. Interestingly, NiDCs preferentially produced the T helper 2 (Th2)-type chemokines macrophage chemotactic protein-1 and macrophage-derived chemokine. These results suggest that the presence of nicotine during differentiation of DCs modulates the immunoregulatory functions of P. gingivalis LPS-stimulated DCs.
authors.affiliation: Department of Periodontology, Division of Oral Biology and Disease Control, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Yanagita
authors.forename: Kenta
authors.initials: K
authors.lastname: Mori
authors.forename: Ryohei
authors.initials: R
authors.lastname: Kobayashi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kojima
authors.forename: Mikiko
authors.initials: M
authors.lastname: Kubota
authors.forename: Koji
authors.initials: K
authors.lastname: Miki
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamada
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kitamura
authors.forename: Shinya
authors.initials: S
authors.lastname: Murakami
mesh_terms: D000704:Analysis of Variance; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D009538:Nicotine / Q000378:metabolism / Q000494:pharmacology*; D010510:Periodontal Diseases / Q000209:etiology* / Q000276:immunology; D016966:Porphyromonas gingivalis / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000378:metabolism
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D009538:Nicotine