S. Buates et G. Matlashewski, Identification of genes induced by a macrophage activator, S-28463, using gene expression array analysis, ANTIM AG CH, 45(4), 2001, pp. 1137-1142
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.