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Department of Biochemistry, Juntendo University, School of Medicine, Tokyo, Japan
The human neutrophil defensins (human neutrophil peptides (HNPs)),
major components of azurophilic granules, contribute to innate and
acquired host immunities through their potent antimicrobial activities
and ability to activate T cells. Despite being encoded by nearly
identical genes, HNP-1 is more abundant in the granules than HNP-3. We
investigated the regulation of HNP-1 and HNP-3 expression at the
transcriptional level using a promyelocytic HL-60 cell line. Luciferase
analysis showed that transcriptional levels of HNP-1 and
HNP-3 promoters were equivalent and that an
200-bp
region identical between promoters was sufficient for transcriptional
activity. Furthermore, overlapping CCAAT/enhancer-binding protein
(C/EBP) and c-Myb sites in the region were found to be required for
efficient transcription. Gel mobility shift assay demonstrated that
C/EBP
predominantly bound to the C/EBP/c-Myb sites using HL-60
nuclear extracts. No specific binding to C/EBP/c-Myb sites was observed
in nuclear extracts from mature neutrophils, which expressed neither
C/EBP
protein nor HNP mRNAs. Taken together, these findings suggest
that the difference in the amounts of HNP-1 and HNP-3 peptides in
neutrophils is caused by posttranscriptional regulation and that
C/EBP
plays an important role in the transcription of
HNP genes in immature myeloid
cells.
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