Document Detail


The human antimicrobial peptide LL-37 suppresses apoptosis in keratinocytes.
MedLine Citation:
PMID:  18923446     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The human cathelicidin antimicrobial peptide LL-37 is involved in various aspects of skin biology, including protection against infection, wound healing, and also in psoriasis. The tight regulation of apoptosis is critical in tissue repair and its deregulation is a part of the psoriasis phenotype. Despite being involved in cell death of several cell types, virtually nothing is known about the function of LL-37 in keratinocyte apoptosis. Here we report that LL-37 peptide protects primary human keratinocytes and HaCaT cells from apoptosis induced by the topoisomerase I inhibitor camptothecin (CAM). In particular, pretreatment with LL-37 significantly decreased caspase-3 activity after CAM-treatment. Expression profiling of keratinocytes treated with LL-37 identified the upregulation of cyclooxygenase-2 (COX-2) expression, a gene implicated in protection from apoptosis. In addition to inducing COX-2 expression, LL-37 stimulated the production of its product, prostaglandin E-2 (PGE-2). Moreover, LL-37 induced the expression of inhibitor of apoptosis-2 (IAP-2), implicated in the COX-2/PGE-2 antiapoptotic pathway. Pretreatment with a selective COX-2 inhibitor abolished the antiapoptotic effect of LL-37 and reduced IAP-2 expression implicating that the antiapoptotic effect of LL-37 in keratinocytes is mediated by a COX-2-dependent mechanism involving IAP-2. Thus, overexpression of LL-37 may contribute to reduced keratinocyte apoptosis in conditions such as psoriasis.
Authors:
Clara I Chamorro; Günther Weber; Alvar Grönberg; Andor Pivarcsi; Mona Ståhle
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Publication Detail:
Type:  Journal Article     Date:  2008-10-16
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  129     ISSN:  1523-1747     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-03-26     Completed Date:  2009-04-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  937-44     Citation Subset:  IM    
Affiliation:
Dermatology and Venereology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Antimicrobial Cationic Peptides / pharmacology*
Apoptosis / drug effects*
Camptothecin / pharmacology
Caspase 3 / antagonists & inhibitors
Cells, Cultured
Cyclooxygenase 2 / genetics,  physiology
Cyclooxygenase 2 Inhibitors / pharmacology
Dinoprostone / biosynthesis
Enzyme Activation / drug effects
Gene Expression Regulation / drug effects
Humans
Inhibitor of Apoptosis Proteins / genetics
Keratinocytes / drug effects*,  metabolism,  pathology
Chemical
Reg. No./Substance:
0/Antimicrobial Cationic Peptides; 0/BIRC3 protein, human; 0/Cyclooxygenase 2 Inhibitors; 0/Inhibitor of Apoptosis Proteins; 143108-26-3/CAP18 lipopolysaccharide-binding protein; 363-24-6/Dinoprostone; 7689-03-4/Camptothecin; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/PTGS2 protein, human; EC 3.4.22.-/Caspase 3
Comments/Corrections
Comment In:
J Invest Dermatol. 2009 Apr;129(4):824-6   [PMID:  19322162 ]
J Invest Dermatol. 2009 Apr;129(4):814   [PMID:  19322157 ]

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