- 一般社団法人 日本炎症・再生医学会
- 炎症・再生 (ISSN:13468022)
- vol.22, no.6, pp.535-541, 2002-11-30 (Released:2010-04-12)
One of the major risk factors triggering or worsening human inflammatory bowel disease (IBD) is the administration of non-steroidal anti-inflammatory drugs (NSAIDs) . Since NSAIDs share inhibition of the enzyme-cyclooxygenase (COX) that catalyzes production of prostanoids, some prostanoids are formed and negatively modulate the extension of IBD. We used mice deficient in prostaglandin (PG) E2 receptor EP1, EP2, EP3, and EP4, and examined the roles of prostaglandin E2 in DSS-induced colitis model. Among the PGE2 receptor-deficient mice, only EP4-deficient mice developed severe colitis with 3% DSS treatment, which induced only marginal colitis in wild-type mice. Conversely, administration of an EP 4-selective agonist (AE 1-734) to wild type mice ameliorated severe colitis normally induced with 7% DSS, while that of an EP 4 agonist, AE 3-208, suppressed recovery from colitis and induced significant proliferation of CD 4+ T cells. In vitro AE 3-208 enhanced and AE 1-734 suppressed the proliferation and Th 1 cytokine production of lamina propria mononuclear cells from the colon. DNA microarray analysis revealed elevated expression of genes associated with immune response and reduced expression of genes with mucosal repair and remodeling in the colon of EP 4-deficient mice. We conclude that EP 4 maintains intestinal homeostasis by keeping mucosal integrity and downregulating immune response.