B-mediated transcriptional regulation of human ß-defensin-2 gene following lipopolysaccharide stimulation
Department of Biochemistry, Juntendo University, School of Medicine, Tokyo, Japan
Correspondence: Isao Nagaoka, M.D., Ph.D., Department of Biochemistry, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 Japan. E-mail: nagaokai{at}med.juntendo.ac.jp
ß-Defensins are cationic peptides with broad-spectrum antimicrobial
activities that contribute to innate host defense. Among human
ß-defensins (hBDs), hBD-2 is up-regulated in epithelial tissues and
mononuclear phagocytes in response to bacterial infection and
proinflammatory cytokines. However, little is known about the molecular
mechanism of hBD-2 gene regulation. Here, we investigated
lipopolysaccharide (LPS)-mediated transcriptional regulation of the
hBD-2 gene by focusing on the roles of NF-
B, STAT, and NF-IL-6 sites
in mononuclear phagocytes using RAW264.7 cells, which are sensitive to
LPS. Luciferase reporter analyses demonstrated that two NF-B sites
were essential for full LPS responsiveness of the hBD-2 gene. Further,
both NF-B sites were also crucial for basal transcriptional
activity. In contrast, neither the NF-IL-6 nor STAT binding site was
required for LPS-induced hBD-2 transcription. Electrophoretic mobility
shift assay indicated that in unstimulated cells, NF-B p50 homodimer
bound to both NF-B sites, whereas the p65-p50 heterodimer formed
complexes with these sites following LPS stimulation. Together, these
observations indicate that NF-B plays an important role in the
regulation of hBD-2 gene expression in response to LPS.
Key Words: antimicrobial peptide • epithelia • macrophage • NF-IL-6 • innate immunity • host defense
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