TY - JOUR
TI - Corticotropin-Releasing factor regulates TLR4 expression in the colon and protects mice from colitis
AU - Chaniotou, Z.
AU - Giannogonas, P.
AU - Theoharis, S.
AU - Teli, T.
AU - Gay, J.
AU - Savidge, T.
AU - Koutmani, Y.
AU - Brugni, J.
AU - Kokkotou, E.
AU - Pothoulakis, C.
AU - Karalis, K.P.
JO - Hepato-Gastroenterology
PY - 2010
VL - 139
TODO - 6
SP - 2083-2092
PB - W.B. Saunders
SN - null
TODO - 10.1053/j.gastro.2010.08.024
TODO - corticotropin releasing factor;  glucocorticoid;  interleukin 12;  prostaglandin E2;  toll like receptor 4, animal experiment;  animal tissue;  article;  cell count;  colitis;  crypt cell;  disease predisposition;  down regulation;  enteritis;  fetus;  histopathology;  innate immunity;  male;  mouse;  nonhuman;  phenotype;  priority journal;  protein expression;  protein function
TODO - Background & Aims Defects in the colonic innate immune response have been associated with inflammatory bowel disease (IBD). Corticotropin-releasing hormone (CRH, or corticotropin-releasing factor [CRF]) is a neuropeptide that mediates the stress response in humans, is an immunomodulatory factor with proinflammatory effects, and regulates transcription of Toll-like receptors (TLR)-2 and TLR4. We investigated the role of CRF in an innate immunitydependent mouse model of IBD. Methods Crh-/- and wild-type (Crh+/+) mice, which are glucocorticoid insufficient, were given dextran sodium sulfate in their drinking water to induce colitis; in some experiments, mice were also given glucocorticoids. Phenotypes of mice were compared; tissues were analyzed by histology and for expression of immune mediators. Results Crh-/- mice had more colonic inflammation than Crh+/+ mice, characterized by reduced numbers of crypts and severe epithelial damage and ulcerations. Colonic tissue levels of the proinflammatory factors interleukin-12 and prostaglandin E2 were increased in the Crh-/- mice. Colons of Crh -/- mice expressed lower levels of Tlr4 than wild-type mice before, but not after, colitis was induced. Administration of glucocorticoid at low levels did not prevent Crh-/- mice from developing severe colitis. Crh-/- mice were unable to recover from acute colitis, as indicated by their increased death rate. Conclusions Mice deficient in CRF down-regulate TLR4 and are more susceptible to dextran sodium sulfateinduced colitis. CRF has anti-inflammatory effects in innate immunitydependent colitis and its recovery phase; these are independent of glucocorticoid administration. CRF might therefore be developed as a therapeutic target for patients with IBD. © 2010 AGA Institute.
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