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Editorial
. 2010 Jan 1;9(1):3-5.
doi: 10.4161/cc.9.1.10352. Epub 2010 Jan 18.

Enterotoxigenic Bacteroides fragilis (ETBF)-mediated colitis in Min (Apc+/-) mice: a human commensal-based murine model of colon carcinogenesis

Franck Housseau, Cynthia L Sears
Editorial

Enterotoxigenic Bacteroides fragilis (ETBF)-mediated colitis in Min (Apc+/-) mice: a human commensal-based murine model of colon carcinogenesis

Franck Housseau et al. Cell Cycle. .
No abstract available

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Figures

Figure 1
Figure 1
STAT-3/TH-17: the missing link between inflammation and carcinogenesis. ETBF is a gram negative bacterium, which is thought to stimulate pattern recognition receptors (PRR ) expressed at the surface of colonic epithelial cells (CEC) and/or immune cells such as interdigiting dendritic cells (DC) present in the lamina propria (LP) of colonic epithelium. This innate signal triggers the inflammatory response to the pathogenic commensal colonization, including the downstream NFκB cascade and the production of pro-inflammatory cytokines such as IL-1β, TNFα and IL-6. ET BF colonization of CECs is accompanied by the production of the Bacteroides fragilis toxin (BFT). BFT triggers the cleavage of E-cadherin and complex signal transduction in CECs involving the β-catenin/Wnt pathway leading to the production of c-Myc and CEC proliferation as well as the release from CECs of cytokines/chemokines including IL-8 and TGFβ. Decreased barrier function due to E-cadherin cleavage facilitates exposure of ETBF to mucosal immune cells such as DCs. BFT is thought to, in part, initiate oncogenesis via specific mechanisms yet to be defined. The paracrine/autocrine expression of IL-6 and STAT-3 activation may play central roles in promoting tumorigenesis via their pro-proliferative, anti-apoptotic and/or pro-angiogenesis properties. IL-6 secretion by and STAT-3 activation in epithelial and immune cells also contribute to diverting local T cell differentiation from a homeostatic regulatory pathway (T-reg) under TGFβ control to a Th17 pro-inflammatory response sustained by the production of key cytokines such as IL-23. IL-17 recruits polymorphonuclear leukocytes (PN; neutrophils) and may promote CEC proliferation through IL-6-dependent activation of STAT-3. The respiratory burst originating from the anti-bacterial activity of PN is known to induce DNA damage and genetic instability, which can also initiate oncogenesis. Chronic asymptomatic ETBF colonization is proposed to cause a persistent Th17 inflammatory colonic response, which promotes CRC genesis, at least in part, through the actions of STAT-3 and IL-6.
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