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* Department of Hematology and Oncology, University of Regensburg, Regensburg, Germany; and
Pulmonary Center, Boston University School of Medicine, Boston, MA 02118
This report investigates the molecular basis for tissue-restricted
and regulated expression of the pattern recognition receptor Toll-like
receptor (TLR)2 in human monocytes and macrophages. To define the
proximal promoter, the full 5'-sequence and transcriptional start sites
of TLR2 mRNA were determined. The human TLR2 gene
was found to consist of two 5' noncoding exons followed by a third
coding exon. Alternative splicing of exon II was detected primarily in
human blood monocytes. The proximal promoter, exon I, and part of
intron I were found to be located in a CpG island. Although CpG
methylation of the proximal human TLR2 promoter in cell lines
correlated with TLR2 repression, the promoter was unmethylated in
primary cells, indicating that CpG methylation does not contribute to
the cell-type specific expression of human TLR2 in normal tissues. The
promoter sequence contains putative binding sites for several
transcription factors, including Sp1 and Ets family members. Reporter
gene analysis revealed a minimal promoter of 220 bp that was found to
be regulated by Sp1, Sp3, and possibly PU.1. Interestingly, no sequence
homology was detected between human and murine TLR2 promoter regions.
In contrast to murine TLR2, expression of human TLR2 in
monocytes/macrophages is not induced by the proinflammatory stimuli LPS
or macrophage-activating lipopeptide-2, and reporter activity of the
promoter was not enhanced by stimuli-induced NF-
B activation in
THP-1 or MonoMac-6 cells. Our findings provide an initial definition of
the human TLR2 promoter and reveal profound differences in the
regulation of an important pattern recognition molecule in humans and
mice.
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