title: Isoflavones, genistein and daidzein, regulate mucosal immune response by suppressing dendritic cell function.
abstract: Lipopolysaccharide (LPS), a component of gram-negative bacterial cell walls, has been shown to have a strong adjuvant effect towards inhaled antigens contributing to airway inflammation. Isoflavones are anti-inflammatory molecules present in abundant quantities in soybeans. We investigated the effect of isoflavones on human dendritic cell (DC) activation via LPS stimulation and subsequent DC-mediated effector cell function both in vitro and in a mouse model of upper airway inflammation. Human monocyte-derived DCs (MDDC) were matured with LPS (or TNF-α) +/- isoflavones (genistein or daidzein). The surface expression levels of DC activation markers were analyzed by flow cytometry. Mature DCs +/- isoflavones were washed and cultured with freshly-isolated allogenic naïve CD4⁺ T cells for 5 days or with autologous natural killer (NK) cells for 2 hours. The percentages of proliferating IFN-γ⁺ CD4⁺ T cells and cytokine levels in culture supernatants were assessed. NK cell degranulation and DC cytotoxicity were measured by flow cytometry. Isoflavones significantly suppressed the activation-induced expression of DC maturation markers (CD83, CD80, CD86) and MHC class I but not MHC class II molecules in vitro. Isoflavone treatment inhibited the ability of LPS-DCs to induce IFN-γ in CD4⁺ T cells. NK cell degranulation and the percentage of dead DCs were significantly increased in isoflavone-treated DC-NK co-culture experiments. Dietary isoflavones suppressed the mucosal immune response to intra-nasal sensitization of mice to ovalbumin. Similar results were obtained when isoflavones were co-administered during sensitization. These results demonstrate that soybean isoflavones suppress immune sensitization by suppressing DC-maturation and its subsequent DC-mediated effector cell functions.
authors.affiliation: The Jaffe Food Allergy Institute, Division of Allergy and Immunology, Department of Pediatrics, Mount Sinai School of Medicine, New York, New York, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Wei
authors.forename: Shiven
authors.initials: S
authors.lastname: Bhatt
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Chang
authors.forename: Hugh A
authors.initials: HA
authors.lastname: Sampson
authors.forename: Madhan
authors.initials: M
authors.lastname: Masilamani
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology* / Q000494:pharmacology; D051940:B7-2 Antigen / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D019833:Genistein / Q000276:immunology / Q000494:pharmacology; D006801:Humans; D018928:Immunity, Mucosal / Q000187:drug effects / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007529:Isoflavones / Q000276:immunology* / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000276:immunology / Q000517:prevention & control; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D051940:B7-2 Antigen; D007529:Isoflavones; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C004742:daidzein; D007371:Interferon-gamma; D010047:Ovalbumin; D019833:Genistein