The gut microbiota engages different signaling pathways to induce Duox2 expression in the ileum and colon epithelium
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The gut microbiota engages different signaling pathways to induce Duox2 expression in the ileum and colon epithelium. / Sommer, F; Bäckhed, Gert Fredrik.
In: Mucosal Immunology, Vol. 8, No. 2, 03.2015, p. 372-9.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The gut microbiota engages different signaling pathways to induce Duox2 expression in the ileum and colon epithelium
AU - Sommer, F
AU - Bäckhed, Gert Fredrik
PY - 2015/3
Y1 - 2015/3
N2 - The epithelium is a first line of defense against microorganisms in the gut. Reactive oxygen species (ROS) have an important role in controlling the normal gut microbiota and pathogenic bacteria. Dual oxidase 2 (DUOX2) is an important source of hydrogen peroxide in the small and large intestine, and the gut microbiota induces Duox2 expression. Here, we investigated the microbial regulation of Duox2 expression. We found that Duox2 was expressed by intestinal epithelial cells mainly in the tip of the epithelium. Duox2 expression was strongly induced by the presence of a normal microbiota in mice, but not when germ-free mice were colonized with various commensal bacteria. Duox2 expression was more rapidly induced by the gut microbiota in the colon than in the ileum. Furthermore, we showed that regulation of Duox2 expression in the ileum involved TIR-domain-containing adaptor protein including interferon-β (TRIF) and canonical nuclear factor-κB p50/p65 signaling, whereas regulation of Duox2 expression in the colon involved MyD88 and the p38 pathway. Collectively, these data indicate that the gut microbiota uses two distinct signaling pathways to induce Duox2 expression in the ileum and colon epithelium.
AB - The epithelium is a first line of defense against microorganisms in the gut. Reactive oxygen species (ROS) have an important role in controlling the normal gut microbiota and pathogenic bacteria. Dual oxidase 2 (DUOX2) is an important source of hydrogen peroxide in the small and large intestine, and the gut microbiota induces Duox2 expression. Here, we investigated the microbial regulation of Duox2 expression. We found that Duox2 was expressed by intestinal epithelial cells mainly in the tip of the epithelium. Duox2 expression was strongly induced by the presence of a normal microbiota in mice, but not when germ-free mice were colonized with various commensal bacteria. Duox2 expression was more rapidly induced by the gut microbiota in the colon than in the ileum. Furthermore, we showed that regulation of Duox2 expression in the ileum involved TIR-domain-containing adaptor protein including interferon-β (TRIF) and canonical nuclear factor-κB p50/p65 signaling, whereas regulation of Duox2 expression in the colon involved MyD88 and the p38 pathway. Collectively, these data indicate that the gut microbiota uses two distinct signaling pathways to induce Duox2 expression in the ileum and colon epithelium.
KW - Animals
KW - Cell Line, Tumor
KW - Colitis
KW - Colon
KW - Epithelial Cells
KW - Female
KW - Gene Expression
KW - Humans
KW - Ileum
KW - Interleukin-1beta
KW - Intestinal Mucosa
KW - Mice
KW - Mice, Knockout
KW - Microbiota
KW - NADPH Oxidase
KW - NF-kappa B
KW - Reactive Oxygen Species
KW - Signal Transduction
KW - p38 Mitogen-Activated Protein Kinases
U2 - 10.1038/mi.2014.74
DO - 10.1038/mi.2014.74
M3 - Journal article
C2 - 25160818
VL - 8
SP - 372
EP - 379
JO - Mucosal Immunology
JF - Mucosal Immunology
SN - 1933-0219
IS - 2
ER -
ID: 156090358