Increased susceptibility to colitis-associated cancer of mice lacking TIR8, an inhibitory member of the interleukin-1 receptor family.
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.
Garlanda
Cecilia
C
Istituto Clinico Humanitas (IRCCS), Rozzano, Italy.
Riva
Federica
F
Veliz
Tania
T
Polentarutti
Nadia
N
Pasqualini
Fabio
F
Radaelli
Enrico
E
Sironi
Marina
M
Nebuloni
Manuela
M
Zorini
Elisabetta Omodeo
EO
Scanziani
Eugenio
E
Mantovani
Alberto
A
D000818:Animals; D003092:Colitis / Q000150:complications*; D003433:Crosses, Genetic; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D007249:Inflammation; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics*; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
D016207:Cytokines; D015232:Dinoprostone; D017472:Receptors, Interleukin-1; C484529:SIGIRR protein, mouse