title: CXCL12 and CXCR4 expression by human gingival fibroblasts in periodontal disease.
abstract: CXCL12 is a CXC chemokine that is related to lymphocyte infiltration and angiogenesis in inflammatory sites such as arthritis. However, the expression and roles of CXCL12 in periodontal disease are uncertain. The aim of this study was to assess the expression of CXCL12 and its receptor, CXCR4, in periodontal tissue and to investigate the properties of CXCL12 and CXCR4 expression by human gingival fibroblasts (HGF). RT-PCR analysis revealed that CXCL12 and CXCR4 mRNA were expressed in both normal gingival tissues and periodontal diseased tissues. Immunohistochemistry disclosed that CXCL12 was expressed and CXCR4 positive cells were found in both normal and periodontal diseased gingival tissues. Our in vitro experiments elucidated that HGF constitutively produced CXCL12, and the levels were enhanced by stimulation with tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta), regulated upon activation normal T cell expressed and secreted (RANTES) and macrophage inflammatory protein 3(alpha) (MIP-3(alpha)). On the other hand, heat killed Porphyromonas gingivalis (P. gingivalis) and P. gingivalis LPS reduced the CXCL12 production by HGF. Flow cytometry analysis clarified that CXCR4 was highly expressed on HGF, and CXCR4 expression was abrogated by TNF-alpha, IFN-gamma and P. gingivalis LPS. Moreover, CXCL12 induced vascular endothelial growth factor (VEGF) production by HGF. Our results demonstrated that CXCL12 might be related to CXCR4+ cells infiltration and angiogenesis both in normal periodontal tissues and periodontal diseased tissue. P. gingivalis, a known periodontal pathogen, inhibits the production of CXCL12 and the expression of CXCR4 by HGF. This fact means that P. gingivalis may inhibit CXCR4+ cells infiltration and neovascularization in periodontal tissue and escape from the immune response.
authors.affiliation: Department of Conservative Dentistry, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, 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: K
authors.initials: K
authors.lastname: Murakami
authors.forename: Y
authors.initials: Y
authors.lastname: Miyake
authors.forename: T
authors.initials: T
authors.lastname: Matsuo
mesh_terms: D002478:Cells, Cultured; D054418:Chemokine CCL20; D018946:Chemokine CCL5 / Q000494:pharmacology; D054377:Chemokine CXCL12; D019742:Chemokines, CC / Q000494:pharmacology; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005434:Flow Cytometry; D005881:Gingiva / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D010510:Periodontal Diseases / Q000378:metabolism* / Q000473:pathology; D016966:Porphyromonas gingivalis / Q000378:metabolism / Q000472:pathogenicity; D012333:RNA, Messenger / Q000032:analysis; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C108355:CCL20 protein, human; C515255:CXCL12 protein, human; D054418:Chemokine CCL20; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D019742:Chemokines, CC; D019743:Chemokines, CXC; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D007371:Interferon-gamma