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

Cecilia Garlanda, Federica Riva, Tania Veliz, Nadia Polentarutti, Fabio Pasqualini, Enrico Radaelli, Marina Sironi, Manuela Nebuloni, Elisabetta Omodeo Zorini, Eugenio Scanziani, Alberto Mantovani

Research output: Contribution to journalArticle

Abstract

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 E2, 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.

Original languageEnglish
Pages (from-to)6017-6021
Number of pages5
JournalCancer Research
Volume67
Issue number13
DOIs
Publication statusPublished - Jul 1 2007

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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