Identification of genes induced by a macrophage activator, S-28463, using gene expression array analysis.
S-28463 and imiquimod are imidazoquinoline compounds which stimulate microbicidal activity by inducing a local immune response at the site of application. Imiquimod-containing cream is an effective clinical treatment against cervical warts caused by human papillomavirus infection. Imiquimod also induces leishmanicidal activity both in vitro in macrophages and in vivo in a mouse model for cutaneous leishmaniasis. The major target cells of S-28463 and imiquimod are macrophages. To explore the molecular basis in which imidazoquinolines generate macrophage microbicidal activity, a cDNA gene array analysis was undertaken to identify genes induced by S-28463. Out of 588 genes screened in this assay, only 13 genes were significantly induced by S-28463. Remarkably, virtually all of the induced genes are involved in macrophage activation and inflammatory response. This experimental approach defines the mechanism of action of this clinically relevant compound in the induction of microbicidal activity in macrophages and also potentially identifies novel genes associated with microbicidal activity in this cell type.
Buates
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Department of Microbiology and Immunology, McGill University, Montreal, Canada H3A 2B4.
Matlashewski
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D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology; D005260:Female; D020869:Gene Expression Profiling; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D008262:Macrophage Activation / Q000187:drug effects* / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis; D015854:Up-Regulation
D000634:Aminoquinolines; D000998:Antiviral Agents; D007375:Interleukin-1; D012333:RNA, Messenger; C099445:S 28463; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse