Document Detail


Effect of the antimicrobial peptide LL-37 on Toll-like receptors 2-, 3- and 4-triggered expression of IL-6, IL-8 and CXCL10 in human gingival fibroblasts.
MedLine Citation:
PMID:  20570250     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The antimicrobial peptide LL-37 is known to have a potent LPS-neutralizing activity in monocytes and macrophages. Recently, LL-37 in gingival crevicular fluids is suggested to be the major protective factor preventing infection of periodontogenic pathogens. In this study, we tried to address the effect of LL-37 on proinflammatory responses of human gingival fibroblasts (HGFs) stimulated with Toll-like receptor (TLR)-stimulant microbial compounds. LL-37 potently suppressed LPS-induced gene expression of IL6, IL8 and CXCL10 and intracellular signaling events, degradation of IRAK-1 and IkappaBalpha and phosphorylation of p38 MAPK and IRF3, indicating that the LPS-neutralizing activity is also exerted in HGFs. LL-37 also suppressed the expression of IL6, IL8 and CXCL10 induced by the TLR3 ligand poly(I:C). LL-37 modestly attenuated the expression of IL6 and IL8 induced by the TLR2/TLR1 ligand Pam(3)CSK(4), but did not affect the expression induced by the TLR2/TLR6 ligand MALP-2. Interestingly, LL-37 rather upregulated the expression of IL6, IL8 and CXCL10 induced by another TLR2/TLR6 ligand FSL-1. Thus, the regulatory effect of LL-37 is differently exerted towards proinflammatory responses of HGFs induced by different microbial stimuli, which may lead to unbalanced proinflammatory responses of the gingival tissue to infection of oral microbes.
Authors:
T Into; M Inomata; K Shibata; Y Murakami
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-15
Journal Detail:
Title:  Cellular immunology     Volume:  264     ISSN:  1090-2163     ISO Abbreviation:  Cell. Immunol.     Publication Date:  2010  
Date Detail:
Created Date:  2010-07-12     Completed Date:  2010-09-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1246405     Medline TA:  Cell Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  104-9     Citation Subset:  IM    
Copyright Information:
2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Oral Microbiology, Asahi University School of Dentistry, 1851-1 Hozumi, Mizuho, Gifu 501-0296, Japan. into@dent.asahi-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Antimicrobial Cationic Peptides / pharmacology*
Bacterial Infections / immunology
Cells, Cultured
Chemokine CXCL10 / biosynthesis*,  genetics,  secretion
Fibroblasts / drug effects*,  immunology,  metabolism,  pathology
Gene Expression Regulation
Gingiva / pathology
Humans
Immunity, Innate
Interleukin-1 Receptor-Associated Kinases / antagonists & inhibitors
Interleukin-6 / biosynthesis*,  genetics,  secretion
Interleukin-8 / biosynthesis*,  genetics,  secretion
Ligands
Periodontal Diseases / immunology
Signal Transduction / drug effects
Toll-Like Receptor 2 / immunology,  metabolism
Toll-Like Receptor 3 / immunology,  metabolism
Toll-Like Receptor 4 / immunology,  metabolism
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
Chemical
Reg. No./Substance:
0/Antimicrobial Cationic Peptides; 0/Chemokine CXCL10; 0/Interleukin-6; 0/Interleukin-8; 0/Ligands; 0/TLR2 protein, human; 0/TLR3 protein, human; 0/TLR4 protein, human; 0/Toll-Like Receptor 2; 0/Toll-Like Receptor 3; 0/Toll-Like Receptor 4; 143108-26-3/CAP18 lipopolysaccharide-binding protein; EC 2.7.11.1/Interleukin-1 Receptor-Associated Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases

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