Infection and Immunity, January 2000, p. 113-119, Vol. 68, No. 1
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Copyright © 2000, American Society for Microbiology. All rights reserved.
-Defensin Gene
Expression in Tracheal Epithelial Cells
Department of Anatomy, Cell Biology and Injury Sciences, UMDNJ-New Jersey Medical School, Newark, New Jersey 071031; Department of Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 191042; and Department of Immunology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 441953
Received 2 August 1999/Returned for modification 22 September 1999/Accepted 5 October 1999
Innate immunity provides an ever-present or rapidly inducible
initial defense against microbial infection. Among the effector molecules of this defense in many species are broad-spectrum
antimicrobial peptides. Tracheal antimicrobial peptide (TAP) was the
first discovered member of the
-defensin family of mammalian
antimicrobial peptides. TAP is expressed in the ciliated epithelium of
the bovine trachea, and its mRNA levels are dramatically increased upon
stimulation with bacteria or bacterial lipopolysaccharide (LPS). We
report here that this induction by LPS is regulated at the level of
transcription. Furthermore, the transfection of reporter gene
constructs into tracheal epithelial cells indicates that DNA sequences
in the 5' flanking region of the TAP gene, within 324 nucleotides of the transcription start site, are responsible in part for mediating gene induction. This region includes consensus binding sites for NF-
B and nuclear factor interleukin-6 (NF IL-6) transcription factors. Gel mobility shift assays indicate that LPS induces NF-
B binding activity in the nuclei of these cells, while NF IL-6 binding activity is constitutively present. The gene encoding human
-defensin 2, a human homologue of TAP with similar inducible
expression patterns in the airway, was cloned and found to have
conserved NF-
B and NF IL-6 consensus binding sites in its 5'
flanking region. Previous studies of antimicrobial peptides from
insects indicated that their induction by infectious microbes and
microbial products also occurs via activation of NF-
B-like and NF
IL-6-like transcription factors. Together, these observations indicate
that a strategy for the induction of peptide-based antimicrobial innate
immunity is conserved among evolutionarily diverse organisms.
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