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.
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.
Into
T
T
Department of Oral Microbiology, Asahi University School of Dentistry, 1851-1 Hozumi, Mizuho, Gifu 501-0296, Japan. into@dent.asahi-u.ac.jp
Inomata
M
M
Shibata
K
K
Murakami
Y
Y
D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001424:Bacterial Infections / Q000276:immunology; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D005881:Gingiva / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D053592:Interleukin-1 Receptor-Associated Kinases / Q000037:antagonists & inhibitors; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D010510:Periodontal Diseases / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000276:immunology / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D054804:Cathelicidins
D023181:Antimicrobial Cationic Peptides; D054357:Chemokine CXCL10; D015850:Interleukin-6; D016209:Interleukin-8; D008024:Ligands; C495342:TLR2 protein, human; C495344:TLR3 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D053592:Interleukin-1 Receptor-Associated Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D054804:Cathelicidins