Nonsteroidal anti-inflammatory drugs increase the severity of human inflammatory bowel disease (IBD), but little is known about the mechanisms by which prostanoid inhibition modulates IBD. In April 1 Journal of Clinical Investigation, Kenji Kabashima and colleagues from Kyoto University, Kyoto, Japan, show that the prostaglandin receptor EP4 has a key role in mucosal protection, suppressing colitis, mucosal damage and CD4 cell activation in the gut.

Kabashima et al. examined mice deficient in prostanoid receptors exposed to dextran sodium sulphate in order to induce colitis. Of the seven types and subtypes of prostanoid receptors they found that only EP4-deficient mice developed severe colitis. EP4 deficiency impaired mucosal barrier function and induced epithelial loss, crypt damage and aggregation of colonic neutrophils and lymphocytes. DNA microarray analysis revealed elevated expression of genes associated with immune response and reduced expression of genes involved in mucosal repair and remodeling in the colon...