Identification of genes induced by a macrophage activator, S-28463, using gene expression array analysis

5-28463 and imiquimod are imidazoquinoline compounds which stimulate microb icidal activity by inducing a local immune response at the site of applicat ion. Imiquimod-containing cream is an effective clinical treatment against cervical warts caused by human papillomavirus infection. Imiquimod also ind uces leishmanicidal activity both in vitro in macrophages and in vivo in a mouse model for cutaneous leishmaniasis. The major target cells of 5-28463 and imiquimod are macrophages, To explore the molecular basis in which imid azoquinolines generate macrophage microbicidal activity, a cDNA gene array analysis was undertaken to identify genes induced by 5-28463, Out of 588 ge nes screened in this assay, only 13 genes were significantly induced by 5-2 8463, Remarkably, virtually all of the induced genes are involved in macrop hage activation and inflammatory response. This experimental approach defin es the mechanism of action of this clinically relevant compound in the indu ction of microbicidal activity in macrophages and also potentially identifi es novel genes associated with microbicidal activity in this cell type.