This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Garlanda, C. Articles by Mantovani, A. Search for Related Content PubMed PubMed Citation Articles by Garlanda, C. Articles by Mantovani, A.

Increased Susceptibility to Colitis-Associated Cancer of Mice Lacking TIR8, an Inhibitory Member of the Interleukin-1 Receptor Family

¹ Istituto Clinico Humanitas (IRCCS), Rozzano, Italy; ² Department of Animal Pathology, Faculty of Veterinary Medicine, ³ Pathology Unit, "L. Sacco" Department of Clinical Sciences, and ⁴ Institute of General Pathology, Faculty of Medicine, University of Milan, Milan, Italy

Requests for reprints: Alberto Mantovani, Istituto Clinico Humanitas, Via Manzoni 56, 20089 Rozzano, Italy. Phone: 39-2-8224-2444; Fax: 39-2-8224-5101; E-mail: alberto.mantovani{at}humanitas.it.

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. [Cancer Res 2007;67(13):6017–21]

This article has been cited by other articles:

				F. Colotta, P. Allavena, A. Sica, C. Garlanda, and A. Mantovani Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability Carcinogenesis, July 1, 2009; 30(7): 1073 - 1081. [Abstract] [Full Text] [PDF]

				K. Bulek, S. Swaidani, J. Qin, Y. Lu, M. F. Gulen, T. Herjan, B. Min, R. A. Kastelein, M. Aronica, M. Kosz-Vnenchak, et al. The Essential Role of Single Ig IL-1 Receptor-Related Molecule/Toll IL-1R8 in Regulation of Th2 Immune Response J. Immunol., March 1, 2009; 182(5): 2601 - 2609. [Abstract] [Full Text] [PDF]

				A. Mantovani Cancer-related Inflammation: The Seventh Hallmark of Cancer ASCO Educational Book, January 1, 2009; 2009(1): 723 - 726. [Abstract] [Full Text] [PDF]

				S. Bozza, T. Zelante, S. Moretti, P. Bonifazi, A. DeLuca, C. D'Angelo, G. Giovannini, C. Garlanda, L. Boon, F. Bistoni, et al. Lack of Toll IL-1R8 Exacerbates Th17 Cell Responses in Fungal Infection J. Immunol., March 15, 2008; 180(6): 4022 - 4031. [Abstract] [Full Text] [PDF]

				M. Dougan and G. Dranoff Inciting inflammation: the RAGE about tumor promotion J. Exp. Med., February 18, 2008; 205(2): 267 - 270. [Abstract] [Full Text] [PDF]