@article{3130716,
    title = "Corticotropin-Releasing factor regulates TLR4 expression in the colon and protects mice from colitis",
    author = "Chaniotou, Z. and Giannogonas, P. and Theoharis, S. and Teli, T. and Gay, J. and Savidge, T. and Koutmani, Y. and Brugni, J. and Kokkotou, E. and Pothoulakis, C. and Karalis, K.P.",
    journal = "Hepato-Gastroenterology",
    year = "2010",
    volume = "139",
    number = "6",
    pages = "2083-2092",
    publisher = "W.B. Saunders",
    doi = "10.1053/j.gastro.2010.08.024",
    keywords = "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",
    abstract = "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."
}