TY - JOUR
T1 - Increased susceptibility to colitis-associated cancer of mice lacking TIR8, an inhibitory member of the interleukin-1 receptor family
AU - Garlanda, Cecilia
AU - Riva, Federica
AU - Veliz, Tania
AU - Polentarutti, Nadia
AU - Pasqualini, Fabio
AU - Radaelli, Enrico
AU - Sironi, Marina
AU - Nebuloni, Manuela
AU - Zorini, Elisabetta Omodeo
AU - Scanziani, Eugenio
AU - Mantovani, Alberto
PY - 2007/7/1
Y1 - 2007/7/1
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-07-0560
DO - 10.1158/0008-5472.CAN-07-0560
M3 - Article
C2 - 17616656
AN - SCOPUS:34447118220
VL - 67
SP - 6017
EP - 6021
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 13
ER -