* Department of Basic Medical Sciences, University of Missouri-Kansas City;
Genetics Institute, Cambridge, Massachusetts; and
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland
Correspondence: Jian Jun Gao, Ph.D., Department of Basic Medical Science, UMKC School of Medicine, 2411 Holmes Street, MC-CO3, Kansas City, MO 64108. E-mail: gaoj{at}umkc.edu
CpG-DNA is known as a potent immunostimulating agent and may contribute in therapeutic treatment of many immune disorders. CpG-DNA triggers innate and acquired immune responses through activated expression of various genes in immune cells, including macrophages. To define the molecular mechanism(s) by which CpG-DNA activates immune cells, we studied macrophage gene expression following CpG-DNA exposure using high-density oligonucleotide microarrays. As CpG-DNA receptor Toll-like receptor 9 (TLR9) shares homology with the lipopolysaccharide (LPS)-TLR4 receptor, we compared gene expression profiles in macrophages stimulated by LPS versus CpG-DNA. CpG-DNA and LPS modulate expression of many genes encoding cytokines, cell surface receptors, transcription factors, and proteins related to cell proliferation/differentiation. However, LPS modulated expression of significantly more genes than did CpG-DNA, and all genes induced or repressed by CpG-DNA were induced or repressed by LPS. We conclude that CpG-DNA signaling through TLR9 activates a subset of genes induced by LPS-TLR4 signaling.
Key Words: cellular activation • gene regulation • inflammation • microarray
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