Abstract
Hematopoietic prostaglandin D synthase (PGDS) is a key enzyme to produce prostaglandin (PG) D and J series. These PGs are involved in inflammation and immune system. While PGD2 mediates sleep and allergic reaction in asthma, the non-enzymatic metabolite, 15-deoxy-Δ12,14-PGJ2 displays several anti-inflammatory effects. Since the PGs are structurally labile and instable in body, constitutive expression of the producing enzyme, PGDS would be expected to evaluate biological activities of PGD2 and PGJ series. To determine whether introduction of PGDS exerts proinflammatory or anti-inflammatory effect, human hematopoietic PGDS complementary DNA-expressing retrovirally transfected fibroblasts were introduced in vivo, and effects of the introduction on several inflammatory models were investigated. Introduction of PGDS-expressing fibroblasts effectively attenuated carrageenin-induced paw edema as an acute inflammatory model and formation of granuloma and angiogenesis in sponge-implanted model as a chronic inflammatory model, suggesting the introduction could be anti-inflammatory. Moreover, expression of PGDS decreased generation of chemokines followed by decreased infiltration of leukocytes in sodium urate monohydrate crystal-induced acute inflammation using air-pouch model in mice, and suppressed fibrosis with reduced expression of cytokines and growth factors in bleomycin-induced lung injury. These results suggest a potential cell therapy for such pathogenesis by PGDS-expressing cells.
