Abstract:
:The human cathelicidin LL-37 is a cationic host defense peptide (antimicrobial peptide) expressed primarily by neutrophils and epithelial cells. This peptide, up-regulated under conditions of inflammation, has immunomodulatory and antimicrobial functions. We demonstrate that LL-37 is a potent inhibitor of human neutrophil apoptosis, signaling through P2X(7) receptors and G-protein-coupled receptors other than the formyl peptide receptor-like-1 molecule. This process involved modulation of Mcl-1 expression, inhibition of BID and procaspase-3 cleavage, and the activation of phosphatidylinositol-3 kinase but not the extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase pathway. In contrast to the inhibition of neutrophil apoptosis, LL-37 induced apoptosis in primary airway epithelial cells, demonstrating alternate consequences of LL-37-mediated modulation of apoptotic pathways in different human primary cells. We propose that these novel immunomodulatory properties of LL-37 contribute to peptide-mediated enhancement of innate host defenses against acute infection and are of considerable significance in the development of such peptides and their synthetic analogs as potential therapeutics for use against multiple antibiotic-resistant infectious diseases.
journal_name
J Leukoc Bioljournal_title
Journal of leukocyte biologyauthors
Barlow PG,Li Y,Wilkinson TS,Bowdish DM,Lau YE,Cosseau C,Haslett C,Simpson AJ,Hancock RE,Davidson DJdoi
10.1189/jlb.1005560subject
Has Abstractpub_date
2006-09-01 00:00:00pages
509-20issue
3eissn
0741-5400issn
1938-3673pii
jlb.1005560journal_volume
80pub_type
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