Prophylactic effects of prostaglandin E2 on NSAID-induced enteropathy - role of EP4 receptors in its protective and healing-promoting effects

Prostaglandin E-2 not only prevents NSAID-generated small intestinal lesions, but also promotes their healing. The protective effects of prostaglandin E-2 are mediated by the activation of EP4 receptors and functionally associated with the stimulation of mucus/fluid secretions and inhibition of intestinal hypermotility, resulting in the suppression of enterobacterial invasion and iNOS up-regulation, which consequently prevents intestinal lesions. Prostaglandin E-2 also promotes the healing of intestinal damage by stimulating angiogenesis through the up-regulation of VEGF expression via the activation of EP4 receptors. These findings have contributed to a further understanding of the mechanisms responsible for 'protective' and 'healing-promoting' effects of prostaglandin E2 and the development of new strategies for the prophylactic treatment of NSAID-induced enteropathy.