Τίτλος:
Corticotropin-Releasing factor regulates TLR4 expression in the colon and protects mice from colitis
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Chaniotou, Z.
Giannogonas, P.
Theoharis, S.
Teli, T.
Gay, J.
Savidge, T.
Koutmani, Y.
Brugni, J.
Kokkotou, E.
Pothoulakis, C.
Karalis, K.P.
Περιοδικό:
Hepato-Gastroenterology
Λέξεις-κλειδιά:
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
DOI:
10.1053/j.gastro.2010.08.024
