title: Nicotine modulates the immunological function of dendritic cells through peroxisome proliferator-activated receptor-γ upregulation.
abstract: We examined the effects of nicotine on differentiation and function of monocyte-derived human dendritic cells (DCs). NiDCs, which were the DCs differentiated in the presence of nicotine, showed lower levels of CD1a. Secretion of IL-12 and TNF-α by lipopolysaccharide (LPS)-stimulated NiDCs was significantly suppressed compared to monocyte-derived DCs grown without nicotine. NiDCs displayed a diminished capacity to induce allogeneic T cell proliferation with a reduced production of IFN-γ, and maintained/enhanced LPS-mediated expression of coinhibitory molecules. Interestingly, NiDCs enhanced the expression of nuclear receptor peroxisome proliferator-activated receptors γ (PPAR γ), which has immunomodulatory properties. Expression of PPAR γ and PPAR γ-target genes was significantly inhibited by pretreatment with d-tubocurarine, antagonist of non-selective nicotinic acetylcholine receptors (nAChR). In addition, reduction of Th1 responses was inhibited after blocking nAChR-mediated signal. These data suggest the effect of nicotine on altering DC immunogenicity by impeding Th1 immunity is partially mediated by upregulation of PPAR γ.
authors.affiliation: Department of Periodontology, Division of Oral Biology and Disease Control, Osaka University Graduate School of Dentistry, Yamadaoka 1-8, Suita, Osaka 565-0871, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Yanagita
authors.forename: Ryohei
authors.initials: R
authors.lastname: Kobayashi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kojima
authors.forename: Kenta
authors.initials: K
authors.lastname: Mori
authors.forename: Shinya
authors.initials: S
authors.lastname: Murakami
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D009000:Monocytes / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D047495:PPAR gamma / Q000096:biosynthesis* / Q000235:genetics; D010641:Phenotype; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014403:Tubocurarine / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D008070:Lipopolysaccharides; D018733:Nicotinic Antagonists; D047495:PPAR gamma; D011978:Receptors, Nicotinic; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D009538:Nicotine; D007371:Interferon-gamma; D014403:Tubocurarine