Isoflavones, Genistein and Daidzein, Regulate Mucosal Immune Response by Suppressing Dendritic Cell Function

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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-?) +/- 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 na?ve CD4+ T cells for 5 days or with autologous natural killer (NK) cells for 2 hours. The percentages of proliferating IFN-?+ 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-? 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. ? 2012 Wei et al.

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Wei, J., Bhatt, S., Chang, L. M., Sampson, H. A., & Masilamani, M. (2012). Isoflavones, Genistein and Daidzein, Regulate Mucosal Immune Response by Suppressing Dendritic Cell Function. PLoS ONE, 7(10). https://doi.org/10.1371/journal.pone.0047979

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