Isoflavones regulate innate immunity and inhibit experimental colitis.
OBJECTIVE
Dysregulated immune responses in the gut to luminal antigens can cause inflammatory bowel diseases (IBD). The roles played by dietary antigens in the pathogenesis or prevention of IBD are poorly understood. Soybean isoflavones are digested in large amounts and have many biological activities. The aim of this study was to determine whether isoflavones in aglycon and bioavailable forms have any effect on gut immunity and protect the host from tissue damage in a mouse model of colitis.


METHODS
We administered daidzein-rich isoflavone aglycones (DRIA) to mice for 1 week and then treated them with 2% dextran sodium sulfate (DSS) in drinking water for 4 days to induce colitis. The effect of DRIA was evaluated by examining the histopathology of the colon, body weight changes, and functional analysis of mesenteric lymph node cells (MLN).


RESULTS
DRIA inhibited interleukin (IL)-6 and IL-8 production by Toll-like receptor (TLR)2, and TLR4-stimulated monocytes in a dose-dependent manner. The mice administered DRIA had less inflammation and tissue damage in the colon than the control mice. This protective effect of DRIA was associated with a decrease in interferon-gamma, IL-6, and IL-12p40 secretion, and an increase in IL-10 secretion and low cell-activation status of antigen-presenting cells (APC) in MLN.


CONCLUSIONS
Ingested DRIA can downregulate the functions of APC and inhibit DSS colitis.
Morimoto
Masakazu
M
Department of Clinical Bio-regulatory Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Watanabe
Tomohiro
T
Yamori
Masashi
M
Takebe
Minoru
M
Wakatsuki
Yoshio
Y
D000818:Animals; D003092:Colitis / Q000188:drug therapy* / Q000276:immunology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology*; D051379:Mice; D018709:Statistics, Nonparametric; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D015850:Interleukin-6; D016209:Interleukin-8; D007529:Isoflavones; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D016753:Interleukin-10; D018664:Interleukin-12; C004742:daidzein; D007371:Interferon-gamma