title: Suppressive effect of the antimicrobial peptide LL-37 on expression of IL-6, IL-8 and CXCL10 induced by Porphyromonas gingivalis cells and extracts in human gingival fibroblasts.
abstract: Porphyromonas gingivalis is a major periodontogenic bacterium and possesses immunostimulatory components, such as lipopolysaccharides (LPS) and fimbriae. The host antimicrobial peptide, LL-37, suppresses proinflammatory responses of immune cells but its effect on human gingival fibroblasts (HGFs) is not known. In this study, we assessed the effect of LL-37 on the proinflammatory responses of HGFs stimulated with P. gingivalis cells and their components. Live P. gingivalis cells did not induce proinflammatory responses of HGFs, and LL-37 did not alter these responses. However, LL-37 was able to suppress the killed P. gingivalis cell-induced secretion of interleukin (IL)-6 and IL-8. LL-37 also suppressed the expression of IL6, IL8, and CXCL10 genes that was induced by P. gingivalis components, including phenol-water extracts, lipid A, and fimbriae, and the induction of phosphorylation of p38 and extracellular signal-regulated kinase (ERK) by P. gingivalis lipopolysaccharide (LPS). CAMP was found to be expressed in oral epithelial cells but not in HGFs, despite stimulation with P. gingivalis components. Therefore, LL-37 can exert a suppressive effect on P. gingivalis-induced proinflammatory responses of HGFs in a paracrine manner, suggesting that excess inflammatory responses to P. gingivalis in the gingival tissue are suppressed by LL-37 in vivo.
authors.affiliation: Department of Oral Microbiology, Asahi University, School of Dentistry, Mizuho, Gifu, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Inomata
authors.forename: Takeshi
authors.initials: T
authors.lastname: Into
authors.forename: Yukitaka
authors.initials: Y
authors.lastname: Murakami
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects* / Q000276:immunology; D010861:Fimbriae, Bacterial / Q000276:immunology; D005881:Gingiva / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000276:immunology; D015850:Interleukin-6 / Q000032:analysis*; D016209:Interleukin-8 / Q000187:drug effects*; D008050:Lipid A / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D009061:Mouth Mucosa / Q000166:cytology / Q000187:drug effects; D019899:Paracrine Communication / Q000187:drug effects; D010766:Phosphorylation; D016966:Porphyromonas gingivalis / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D008050:Lipid A; D008070:Lipopolysaccharides; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D054804:Cathelicidins