Abstract
Triggering receptor expressed on myeloid cells(TREM)-1 is a cell surface molecule that has been identified on monocytes and neutrophils and is implicated in the early inflammatory response induced by microbes. However, it has been remained unclear how the expression of TREM-1 is regulated in non-microbial inflammatory diseases. This study was undertaken to evaluate the biologic role of TREM-1 in the initiation of acute attacks of gout. We investigated TREM-1 expression by monosodium urate monohydrate(MSU) crystal-stimulated resident murine peritoneal macrophages(RPM), and assessed whether TREM-1 signaling amplified response to MSU crystals. TREM-1 expression by RPM stimulated with various inflammatory agents was determined by quantitative real-time PCR and western blot analysis. Cytokine production by RPM cultured with both anti-TREM-1 agonist antibody and MSU crystals was assayed by ELISA. TREM-1 expression was significantly induced in RPM by MSU crystals. The peaks of TREM-1 transcript and product occurred rapidly after 1 and 4 hours of MSU crystal stimulation, respectively. The level of TREM-1 transcript induced was consistent with the result obtained using LPS, a potent TREM-1 inducer. Induction of TREM-1 by anti-TREM-1 agonist Ab and MSU crystals synergistically increased production of IL-1 β and MCP-1 by RPM compared with MSU crystals alone. These findings indicate that rapid induction of TREM-1 expression in RPM by MSU crystals may contribute to the onset of acute gouty arthritis, followed by induction of proinflammatory cytokines.
