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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.

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 and Davidson, Donald J (2006) The human cationic host defense peptide LL-37 mediates contrasting effects on apoptotic pathways in different primary cells of the innate immune system. Journal of Leukocyte Biology, 80 (3). pp. 509-520. ISSN 0741-5400

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Abstract/Description

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.

Item Type: Article
Print ISSN: 0741-5400
Uncontrolled Keywords: cathelicidin ;antimicrobial peptide; neutrophil; epithelial cell; FPRL-1; P2X7
University Divisions/Research Centres: Faculty of Health, Life & Social Sciences > School of Health and Social Sciences
Dewey Decimal Subjects: 600 Technology > 610 Medicine & health > 616 Diseases
Library of Congress Subjects: R Medicine > RB Pathology
Item ID: 5181
Depositing User: Mrs Lyn Gibson
Date Deposited: 27 Mar 2012 14:01
Last Modified: 27 Mar 2012 14:01
URI: http://researchrepository.napier.ac.uk/id/eprint/5181

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