Regulation of gene expression in mouse macrophages stimulated with bacterial CpG-DNA and lipopolysaccharide.
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.
Gao
Jian Jun
JJ
Department of Basic Medical Sciences, University of Missouri-Kansas City, 64108, USA. gaoj@umkc.edu
Diesl
Veronica
V
Wittmann
Tatiana
T
Morrison
David C
DC
Ryan
John L
JL
Vogel
Stefanie N
SN
Follettie
Maximillian T
MT
D000818:Animals; D002460:Cell Line; D004269:DNA, Bacterial / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000502:physiology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000502:physiology; D015398:Signal Transduction; D051217:Toll-Like Receptor 9
C472452:CpG-DNA, E coli; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D011956:Receptors, Cell Surface; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9