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: John Wei, Shiven Bhatt, Lisa M Chang, Hugh A Sampson, Madhan Masilamani
• Journal: PloS one (PLoS One) Vol. 7 Issue 10 Pg. e47979 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 23110148 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• B7-2 Antigen
• Isoflavones
• Lipopolysaccharides
• Toll-Like Receptor 4
• Tumor Necrosis Factor-alpha
• daidzein
• Interferon-gamma
• Ovalbumin
• Genistein

Topics

• Animals
• Anti-Inflammatory Agents (immunology, pharmacology)
• B7-2 Antigen (immunology, metabolism)
• CD4-Positive T-Lymphocytes (drug effects, immunology, metabolism)
• Cell Differentiation (drug effects, immunology)
• Cells, Cultured
• Coculture Techniques
• Dendritic Cells (drug effects, immunology, metabolism)
• Female
• Flow Cytometry
• Genistein (immunology, pharmacology)
• Humans
• Immunity, Mucosal (drug effects, immunology)
• Interferon-gamma (immunology, metabolism)
• Isoflavones (immunology, pharmacology)
• Killer Cells, Natural (drug effects, immunology, metabolism)
• Lipopolysaccharides (immunology, pharmacology)
• Mice
• Mice, Inbred BALB C
• Monocytes (drug effects, immunology, metabolism)
• Ovalbumin (immunology)
• Pneumonia (immunology, prevention & control)
• Toll-Like Receptor 4 (immunology, metabolism)
• Tumor Necrosis Factor-alpha (immunology, pharmacology)