Signal transducer and activator of transcription 5b promotes mucosal tolerance in pediatric Crohn's disease and murine colitis

Academic Article


  • Growth hormone (GH) regulates anabolic metabolism via activation of the STAT5b transcription factor and reduces mucosal inflammation in colitis. Peroxisome proliferator-activated receptor (PPAR) γ suppresses mucosal inflammation and is regulated by GH through STAT5b. We hypothesized that the GH:STAT5b axis influences susceptibility to colitis via regulation of local PPARγ abundance. Colon biopsies from children with newly diagnosed Crohn's disease (CD) and controls were exposed to GH in short-term organ culture. Trinitrobenzene sulfonic acid (TNBS) administration was used to induce colitis in STAT5b-deficient mice and wildtype controls, with and without rosiglitazone pretreatment. GH receptor, STAT5b, PPARγ, and nuclear factor κB activation and expression were determined. Epithelial cell GH receptor expression and GH-dependent STAT5b activation and PPARγ expression were reduced in CD colon. STAT5b-deficient mice exhibited reduced basal PPARγ nuclear abundance and developed more severe proximal colitis after TNBS administration. This was associated with a significant increase in mucosal nuclear factor κB activation at baseline and after TNBS administration. Rosiglitazone ameliorated colitis in wild-type mice but not STAT5b-deficient mice. GH-dependent STAT5b activation is impaired in affected CD colon and contributes to chronic mucosal inflammation via down-regulation of local PPARγ expression. Therapeutic activation of the GH:STAT5b axis therefore represents a novel target for restoring both normal anabolic metabolism and mucosal tolerance in CD. Copyright © American Society for Investigative Pathology.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Han X; Osuntokun B; Benight N; Loesch K; Frank SJ; Denson LA
  • Start Page

  • 1999
  • End Page

  • 2013
  • Volume

  • 169
  • Issue

  • 6