Although the inflammatory bowel diseases – ulcerative colitis and Crohn’s disease – have distinct patterns of injury and inflammation, the existing therapies are quite similar and no therapies specifically target the Th2 immune response activated in ulcerative colitis.
The signaling molecule IL-13 (a key Th2 cytokine) has been implicated in the pathogenesis of the disease, but no group has demonstrated evidence of increased IL-13 signaling in colon tissues of patients with the disease. Michael Rosen, assistant professor of pediatrics, and colleagues now show that STAT6, the key transcription factor activated by IL-13, is activated in colon tissue from pediatric patients recently diagnosed with ulcerative colitis. In cell experiments, they found that STAT6 is involved in IL-13-induced epithelial cell death and barrier disruption, and that blocking STAT6 with the FDA-approved histone deacetylase inhibitor suberoylanilde hydroxamic acid (SAHA) inhibits these effects.
The results, published in the November issue of Inflammatory Bowel Diseases, suggest that compounds targeting STAT6 may have therapeutic promise in ulcerative colitis.
