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The human cationic host defense peptide LL‐37 mediates contrasting effects on apoptotic pathways in different primary cells of the innate immune system
Author(s) -
Barlow Peter G.,
Li Yuexin,
Wilkinson Thomas S.,
Bowdish Dawn M. E.,
Lau Y. Elaine,
Cosseau Celine,
Haslett Christopher,
Simpson A. John,
Hancock Robert E. W.,
Davidson Donald J.
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1005560
Subject(s) - cathelicidin , biology , innate immune system , microbiology and biotechnology , signal transduction , receptor , antimicrobial peptides , inflammation , apoptosis , kinase , beta defensin , peptide , pattern recognition receptor , immunology , biochemistry
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.