There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Abstract
Cathelicidins are a class of small cationic peptide antibiotics that are expressed
in skin and in other epithelial cells and are an active component of mammalian innate
immunity. Human cathelicidin (hCAP18/LL-37) consists of a conserved prosequence called
the cathelin-like domain and a C-terminal peptide named LL-37. To date, our understanding
of the cathelin-like domain was very limited. To bring insight into the function of
this evolutionarily conserved prosequence, we produced recombinant human cathelin-like
protein and full-length hCAP18/LL-37 in Escherichia coli. As the cathelin-like protein
shares homology with the cystatin family of cysteine protease inhibitors, we first
analyzed the effect of the cathelin-like recombinant protein on the cysteine protease
cathepsin L. We found that the cathelin-like protein inhibited protease activity.
Next, we tested the cathelin-like protein for antimicrobial activity using solid phase
radial diffusion and liquid phase killing assays. The cathelin-like prosequence, but
not full-length hCAP18/LL-37, killed human pathogens including E. coli and methicillin-resistant
Staphylococcus aureus at concentrations ranging from 16 to 32 microM. Together these
findings suggest that after proteolytic cleavage the cathelin-like domain can contribute
to innate host defense through inhibition of bacterial growth and limitation of cysteine-proteinase-mediated
tissue damage. As these dual functions are complementary to the LL-37 peptide released
from the C-terminus of full-length hCAP18/LL-37, human cathelicidin represents an
elegant multifunctional effector molecule for innate immune defense of the skin.