A pro-resolution mediator prostaglandin D2 is specifically up-regulated in individuals in long-term remission from ulcerative colitis

摘要

Patients with ulcerative colitis (UC) experience unpredictable bouts of active inflammation and ulceration. Relatively little attention has been paid to the role of antiinflammatory mediators in the pathogenesis of UC, although rodent studies suggest an important role of prostaglandin (PG) D2 in the resolution of tissue injury and inflammation. The present study was performed to determine if colonic PGD2 synthesis was altered in patients in remission from UC and if expression of the key enzymes and receptors related to PGD2 was altered. During routine colon-cancer screening, colonic biopsies were obtained from healthy individuals, some of whom had been in remission from UC, without treatment, for >4 y. UC patients with active disease or in medically induced remission were also biopsied. Only patients with active UC exhibited elevated expression of several proinflammatory cytokines (TNFα and IFNγ) and colonic PGE2 synthesis. In contrast, colonic PGD2 synthesis was only elevated (∼3-fold) in the healthy individuals with a prior history of UC. This group also exhibited significantly elevated expression of DP1, the key receptor mediating the antiinflammatory actions of PGD2. Expression of the synthetic enzymes cyclooxygenase-1, cyclooxygenase-2, and hematopoietic PGD synthase was not altered in the healthy individuals with a prior history of UC. These results show a marked up-regulation of synthesis of an antiinflammatory prostanoid and expression of its receptor, specifically in individuals in long-term remission from UC. This is consistent with animal studies showing the importance of PGD2 in the induction and maintenance of remission from colitis.