| First Author | Karrasch T | Year | 2007 |
| Journal | J Immunol | Volume | 178 |
| Issue | 10 | Pages | 6522-32 |
| PubMed ID | 17475882 | Mgi Jnum | J:146107 |
| Mgi Id | MGI:3836696 | Doi | 10.4049/jimmunol.178.10.6522 |
| Citation | Karrasch T, et al. (2007) Gnotobiotic IL-10-/-;NF-kappa B(EGFP) mice reveal the critical role of TLR/NF-kappa B signaling in commensal bacteria-induced colitis. J Immunol 178(10):6522-32 |
| abstractText | Commensal bacteria and TLR signaling have been associated with the maintenance of intestinal homeostasis in dextran sodium sulfate-induced intestinal injury. The aim of this study was to determine the in vivo role of TLR/NF-kappaB activation in a model of commensal bacteria-induced T cell-mediated colitis. A NF-kappaB reporter gene mouse (NF-kappaBEGFP) (EGFP, enhanced GFP) was crossed to the colitogenic susceptible strain IL-10-/- and derived into germfree conditions using embryo-transfer technology. Germfree IL-10wt/wt;NF-kappaBEGFP and IL-10-/-;NF-kappaBEGFP mice (wt, wild type) were dual associated with the nonpathogenic commensal bacteria strains Enterococcus faecalis and Escherichia coli. EGFP was detected using macroimaging, confocal microscopy, and flow cytometry. IL-10-/-;MyD88-/- mice were used to assess E. faecalis/E. coli-induced TLR-dependent signaling and IL-23 gene expression. Dual-associated IL-10-/-;NF-kappaBEGFP mice developed severe inflammation by 7 wk. Macroscopic analysis showed elevated EGFP expression throughout the colon of bacteria-associated IL-10-/-;NF-kappaBEGFP mice. Confocal microscopy analysis revealed EGFP-positive enterocytes during the early phase of bacterial colonization (1 wk) in both IL-10wt/wt and IL-10-/- mice, while the signal shifted toward lamina propria T cells, dendritic cells, neutrophils, and macrophages in IL-10-/- mice during colitis (7 wk). The NF-kappaB inhibitor BAY 11-7085 attenuated E. faecalis/E. coli-induced EGFP expression and development of colitis. Additionally, E. faecalis/E. coli-induced NF-kappaB signaling and IL-23 gene expression were blocked in bone marrow-derived dendritic cells derived from IL-10-/-;MyD88-/- mice. We conclude that bacteria-induced experimental colitis involves the activation of TLR-induced NF-kappaB signaling derived mostly from mucosal immune cells. Blocking TLR-induced NF-kappaB activity may represent an attractive strategy to treat immune-mediated intestinal inflammation. |
