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Triggering receptor expressed on myeloid cells 1 (TREM‐1) is a cell surface molecule that was recently identified on monocytes and neutrophils. TREM‐1 has been implicated in the early inflammatory responses induced by microbes, but its pathophysiologic role in nonmicrobial inflammation remains unknown. In the present study, we investigated the role of TREM‐1 in acute inflammation induced by monosodium urate monohydrate (MSU) crystals. Induction of TREM‐1 expression by MSU crystal–stimulated murine resident peritoneal macrophages and infiltrating leukocytes in a murine air‐pouch model of crystal‐induced acute inflammation was determined. The biologic role of TREM‐1 in crystal‐induced cytokine production by resident peritoneal macrophages was also investigated.TREM‐1 expression by resident peritoneal macrophages and infiltrating leukocytes in a murine air‐pouch model was determined by quantitative real‐time polymerase chain reaction, Western blot analysis, and flow cytometry. Cytokine production by resident peritoneal macrophages after incubation with MSU crystals in the presence or absence of an anti–TREM‐1 agonist antibody was determined by enzyme‐linked immunosorbent assay.TREM‐1 expression by resident peritoneal macrophages was significantly induced after stimulation with the crystals. Maximum expression of TREM‐1 transcripts and protein occurred at 1 and 4 hours after exposure to the crystals, respectively. Costimulation of resident peritoneal macrophages with MSU crystals and an anti–TREM‐1 agonist antibody synergistically increased the production of both interleukin‐1β and monocyte chemotactic protein 1 compared with stimulation with the crystals alone. MSU crystals also induced TREM‐1 expression in infiltrating leukocytes in a murine air‐pouch model of crystal‐induced acute inflammation.These findings suggest that rapid induction of TREM‐1 expression on resident peritoneal macrophages and neutrophils by MSU crystals may contribute to the development of acute gout through enhancement of inflammatory responses. [ABSTRACT FROM AUTHOR]

Hematopoietic prostaglandin D synthase (H-PGDS) is a key enzyme in the production of prostaglandin D and its J series metabolites. We evaluated the antiinflammatory effect of retrovirally transfected H-PGDS in order to investigate the role of H-PGDS in monosodium urate monohydrate (MSU) crystal–induced acute inflammation. Expression of endogenous PGDS in a murine air-pouch model of MSU crystal–induced acute inflammation was determined by real-time polymerase chain reaction. H-PGDS complementary DNA (cDNA) was retrovirally transfected into C57BL/6J fibroblasts, and the cells were designated as C57-PGDS cells. Production of prostaglandins by C57-PGDS cells was measured by enzyme immunoassay. The effect of C57-PGDS cells on crystal-induced inflammation was investigated. Injection of the crystals caused a rapid decrease in H-PGDS expression by infiltrating cells and by the soft tissues around the air pouches. In contrast, expression of interleukin-1β (IL-1β) and macrophage inflammatory protein 2 (MIP-2) as well as cellular infiltration were significantly increased during the early stage of inflammation. C57-PGDS cells, but not control cells, produced an increased amount of PGD2 in vitro, but suppressed production of PGE2. Injection of C57-PGDS cells into air pouches inhibited cellular infiltration and MIP-2 and IL-1β expression. In this murine air-pouch model of MSU crystal–induced inflammation, retrovirally transfected H-PGDS cDNA could reduce cellular infiltration, at least partly by inhibiting MIP-2 and IL-1β. These findings suggest that gene therapy with H-PGDS may be useful for treating inflammatory diseases. [ABSTRACT FROM AUTHOR]