The role of schlafen in macrophages and inflammation

Macrophages are essential for host defence, but when excessively and persistently activated, these cells contribute to the initiation and progression of inflammatory diseases such as rheumatoid arthritis. Investigating the function of inflammatory genes in macrophages may identify novel therapeutic targets for inflammatory diseases. One family of transcripts that are highly expressed in activated macrophages are members of the Schlafen (Slfn) gene family; a recently identified family whose function is still unknown. This study examined the mRNA expression of Slfn in activated bone marrowderived macrophages in vitro, and in collagen-induced arthritis (CIA) in vivo. Real-time PCR expression analyses of bone marrow-derived macrophages stimulated with lipopolysaccharide (LPS) over a time course, revealed differential expression of individual Slfn family genes. In particular, Slfn-1, Slfn-2, and Slfn-4 were maximally induced after 24 hours. The maximal induction of Slfn-8 and Slfn-9 was observed after 4 hours of LPS treatment. Individual members of the Slfn family were also differentially expressed in CIA, a model of rheumatoid arthritis. mRNA levels of Slfn-1, Slfn-2, Slfn-4 and Slfn-5 were elevated in joints affected by CIA. To investigate the role of Slfn-4, we have generated a transgenic mouse line, which over expresses Slfn-4 specifically in cells of the mononuclear phagocyte system, by using a novel binary expression based on the c-fms promoter and Gal4. Further characterisation of the Slfn-4 over expressing mouse line will be used to assess the function of Slfn-4 in macrophage biology and inflammation, and its potential as a therapeutic target