title: Increase of CCL20 expression by human gingival fibroblasts upon stimulation with cytokines and bacterial endotoxin.
abstract: We have demonstrated recently that CCL20 was expressed in periodontal diseased tissues and abundant CCR6 positive T cells infiltrated in periodontally diseased tissue. However, it is uncertain which cells can elicit CCL20 production. In the present study, we examined the properties of CCL20 production by human gingival fibroblasts (HGF) culture. Here, we report that interleukin-1 beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and Escherichia coli lipopolysaccharide (LPS) can significantly induce the production of CCL20 by HGF. We found that TNF-alpha and E. coli LPS enhanced the production of CCL20 by HGF treated with IL-1beta. In contrast, interferon-gamma (IFN-gamma) dramatically diminished CCL20 production induced by IL-1beta. Moreover, we demonstrated that nuclear factor-kappaB (NF-kappaB), p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases (ERK) play an important role in mediating the production of CCL20 induced by IL-1beta and TNF-alpha. On the other hand, we found that not only NF-kappaB, p38 MAPK and ERK but also c-Jun NH2-terminal kinase (JNK) are involved in CCL20 production induced by E. coli LPS. Finally, we found that HGF express CCR6, CCL20 receptor, and CCL20 induced vascular endothelial growth factor (VEGF) by HGF. Taken together, these findings that HGF will be a source of CCL20 in periodontal tissue, and the CCL20 production will be controlled by proinflammatory cytokine and bacterial LPS in periodontally diseased tissue. Thus, CCL20 by HGF might be involved in inflammatory cells infiltration, and promote the progression of periodontal disease.
authors.affiliation: Department of Conservative Dentistry, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan. hosokawa@dent.tokushima-u.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Hosokawa
authors.forename: I
authors.initials: I
authors.lastname: Hosokawa
authors.forename: K
authors.initials: K
authors.lastname: Ozaki
authors.forename: H
authors.initials: H
authors.lastname: Nakae
authors.forename: T
authors.initials: T
authors.lastname: Matsuo
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000235:genetics; D016207:Cytokines / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology; D005260:Female; D005347:Fibroblasts / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D005881:Gingiva / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007375:Interleukin-1 / Q000276:immunology; D048031:JNK Mitogen-Activated Protein Kinases / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology
chemical_list: C108355:CCL20 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D016207:Cytokines; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D007371:Interferon-gamma; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases