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Publication : Increased susceptibility to colitis-associated cancer of mice lacking TIR8, an inhibitory member of the interleukin-1 receptor family.

First Author  Garlanda C Year  2007
Journal  Cancer Res Volume  67
Issue  13 Pages  6017-21
PubMed ID  17616656 Mgi Jnum  J:122829
Mgi Id  MGI:3715576 Doi  10.1158/0008-5472.CAN-07-0560
Citation  Garlanda C, et al. (2007) Increased susceptibility to colitis-associated cancer of mice lacking TIR8, an inhibitory member of the interleukin-1 receptor family. Cancer Res 67(13):6017-21
abstractText  TIR8 (also known as SIGIRR) is a member of the interleukin-1/Toll-like receptor family with inhibitory activity on inflammatory reactions and high expression in intestinal mucosa. Here, we report that Tir8-deficient mice exhibited a dramatic intestinal inflammation in response to dextran sulfate sodium salt (DSS) administration in terms of weight loss, intestinal bleeding, and mortality and showed increased susceptibility to carcinogenesis in response to azoxymethane and DSS. Increased susceptibility to colitis-associated cancer was associated to increased permeability and local production of prostaglandin E(2), proinflammatory cytokines, and chemokines. Thus, these results are consistent with the hypothesis that TIR8, by negatively regulating intestinal inflammation, plays a nonredundant role in the control of the protumor activity of chronic inflammation in the gut.
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