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.

Increased susceptibility to colitis-associated cancer of mice lacking TIR8, an inhibitory member of the interleukin-1 receptor family / C. Garlanda, F. Riva, T. Veliz, N. Polentarutti, F. Pasqualini, E. Radaelli, M. Sironi, M. Nebuloni, E. Omodeo Zorini, E. Scanziani, A. Mantovani. - In: CANCER RESEARCH. - ISSN 0008-5472. - 67:13(2007), pp. 6017-6021.

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

F. Riva
Secondo
;
M. Nebuloni;E. Omodeo Zorini;E. Scanziani
Penultimo
;
A. Mantovani
Ultimo
2007

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 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.
Settore VET/03 - Patologia Generale e Anatomia Patologica Veterinaria
Settore MED/04 - Patologia Generale
Settore VET/05 - Malattie Infettive degli Animali Domestici
Settore MED/08 - Anatomia Patologica
2007
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/37719
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