NOVEL DEFENSINS IN HUMAN EPITHELIAL TISSUE

Project: Research project

Project Details

Description

Despite many significant advances in its prevention and management,
infectious disease still accounts for considerable morbidity and
mortality. The mechanisms by which mammals, including humans defend
against microbial invasion are incompletely defined. Defensins are
recently identified cysteine-rich, cationic peptides found in
abundance in phagocytic leukocytes of several mammals. These peptides
are responsible, in part, for the non-oxidative microbicidal activity
of these cells toward microorganisms. Four defensins, all derived
from granular leukocytes are known to exist in humans. In vitro,
defensins have potent activity against bacteria, fungi and enveloped
viruses. Recent studies in animal models have found that in addition
to leukocytes, epithelial cells also express defensin-related
molecules.
Preliminary studies presented in this proposal show clear evidence of
novel defensin gene expression in non-hematopoietic tissue of humans.
Using a molecular biological approach, strong data have been obtained
indicating that the family of human defensins is more diverse than
currently appreciated, and some of these newly. discovered defensins
are expressed exclusively in epithelial cells. The long range goal of
this research is to define the role of epithelial defensins in host
defense. Toward this goal the following experiments are proposed: 1) Clone and
characterize genes corresponding to the non-hematopoietic defensins,
establish the nucleotide sequence of selected genes and their flanking
sequences, and determine a regional map of these genes which appear to
be clustered; 2) Clone and characterize the cDNA encoding novel
defensins and defensin-related peptide(s) from non-hematopoietic human
tissues; 3) Characterize the cellular localization and antimicrobial
properties of the newly discovered defensins; 4) Identify and
characterize the cis-acting elements which regulate defensin
expression. Epithelial-derived defensins are likely to equip mucosa] surfaces with
a previously unrecognized defensive capability that complements other
well-defined antimicrobial defenses. The understanding of the
physiological regulation of epithelial defensins in humans may
ultimately lead to therapeutic modulation of endogenous peptide
expression, and may lead to the development of novel therapeutic
antimicrobial peptides.
StatusFinished
Effective start/end date7/1/931/31/20

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $259,473.00
  • National Institutes of Health: $395,865.00
  • National Institutes of Health: $244,577.00
  • National Institutes of Health: $382,455.00
  • National Institutes of Health: $314,701.00
  • National Institutes of Health: $320,795.00
  • National Institutes of Health: $202,483.00
  • National Institutes of Health: $314,701.00
  • National Institutes of Health: $286,652.00
  • National Institutes of Health: $251,916.00
  • National Institutes of Health: $329,313.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $208,182.00

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)

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