title: Toll-like receptor 4 regulates colitis-associated adenocarcinoma development in interleukin-10-deficient (IL-10(-/-)) mice.
abstract: Chronic inflammatory conditions such as ulcerative colitis and Crohn's disease are associated with an increased risk of developing adenocarcinoma. It has been hypothesized that this increased risk may be related to soluble mediators present in the inflammatory environment and that factors involved in exacerbating the inflammatory response could increase the risk of developing colitis-associated cancer. There is a growing body of evidence from both clinical studies and animal models which suggests that colitis occurs due to an aberrant immune response to enteric flora in genetically susceptible individuals. It is well documented that bacterial toxins such as endotoxin have potent pro-inflammatory effects through activation of TLR4 (Toll-like receptor 4) and therefore this molecule could potentially play a prominent role in the initiation/exacerbation of colitis and adenocarcinoma development. Using genetic mutant mice, we have examined the role of TLR4 in a spontaneously developing mouse model of colitis-associated adenocarcinoma: the IL-10(-/-) (interleukin-10-deficient) mouse. Surprisingly, our evidence suggests that the absence of TLR4 promotes colitis-associated adenocarcinoma in IL-10(-/-) mice. TLR4-dependent chemokine induction may play a part in modulating the development of colitis-associated neoplasia through altered leucocyte recruitment.
authors.affiliation: Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada, T2N 4N1.
authors.forename: R
authors.initials: R
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: P L
authors.initials: PL
authors.lastname: Beck
authors.forename: D-M
authors.initials: DM
authors.lastname: McCafferty
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000818:Animals; D003092:Colitis / Q000235:genetics / Q000473:pathology*; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D051197:Toll-Like Receptor 4 / Q000502:physiology*
chemical_list: D051197:Toll-Like Receptor 4; D016753:Interleukin-10