TY - JOUR
T1 - Interleukin 37 expression protects mice from colitis
AU - McNamee, Eoin
AU - Masterson, Joanne
AU - Jedlicka, Paul
AU - McManus, Martine
AU - Grenz, Almut
AU - Collins, Colm
AU - Nold, Marcel
AU - Nold, Claudia
AU - Bufler, Philip
AU - Dinarello, Charles
AU - Rivera-Nieves, Jesus
PY - 2011
Y1 - 2011
N2 - IL-37, a newly described member of the IL-1 family, functions as a fundamental inhibitor of innate inflammation and immunity. In the present study, we examined a role for IL-37 during experimental colitis. A transgenic mouse strain was generated to express human IL-37 (hIL-37tg), and these mice were subjected to dextran sulfate sodium (DSS)-induced colitis. Despite the presence of a CMV promoter to drive expression of IL-37, mRNA transcripts were not present in colons at the resting state. Expression was observed only upon disruption of the epithelial barrier, with a six- to sevenfold increase (P = 0.02) on days 3 and 5 after continuous exposure to DSS. During the development of colitis, clinical disease scores were reduced by 50 (P <0.001), and histological indices of colitis were one-third less in hIL-37tg mice compared with WT counterparts (P <0.001). Reduced inflammation was associated with decreased leukocyte recruitment into the colonic lamina propria. In addition, release of IL-1beta and TNFalpha from ex vivo colonic explant tissue was decreased 5- and 13-fold, respectively, compared with WT (P
AB - IL-37, a newly described member of the IL-1 family, functions as a fundamental inhibitor of innate inflammation and immunity. In the present study, we examined a role for IL-37 during experimental colitis. A transgenic mouse strain was generated to express human IL-37 (hIL-37tg), and these mice were subjected to dextran sulfate sodium (DSS)-induced colitis. Despite the presence of a CMV promoter to drive expression of IL-37, mRNA transcripts were not present in colons at the resting state. Expression was observed only upon disruption of the epithelial barrier, with a six- to sevenfold increase (P = 0.02) on days 3 and 5 after continuous exposure to DSS. During the development of colitis, clinical disease scores were reduced by 50 (P <0.001), and histological indices of colitis were one-third less in hIL-37tg mice compared with WT counterparts (P <0.001). Reduced inflammation was associated with decreased leukocyte recruitment into the colonic lamina propria. In addition, release of IL-1beta and TNFalpha from ex vivo colonic explant tissue was decreased 5- and 13-fold, respectively, compared with WT (P
UR - http://www.pnas.org/content/108/40/16711.full.pdf+html
U2 - 10.1073/pnas.1111982108
DO - 10.1073/pnas.1111982108
M3 - Article
SN - 0027-8424
VL - 108
SP - 16711
EP - 16716
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 40
ER -