title: Modulation of stromal cell-derived factor 1 alpha (SDF-1α) and its receptor CXCR4 in Porphyromonas gingivalis-induced periodontal inflammation.
abstract: BACKGROUND
  The production of chemokines by tissue resident cells during inflammation is considered one of the main mechanisms involved in the formation of inflammatory infiltrates. Fibroblasts are the main resident cell type in gingival and periodontal ligament tissues, and their ability to produce chemokine stromal cell-derived factor 1 alpha (SDF-1α) and its receptor CXCR4 under stimulation by gram negative bacteria, Porphyromonas gingivalis, commonly found in periodontal infections was investigated.
  
  
  METHODS
  Western blots were used to assess SDF-1α and CXCR4 protein expression levels in human gingival fibroblast cells (HGF-1) induced by Lipopolysaccharide (LPS) from P. gingivalis in the presence or absence of LY294002, a highly selective inhibitor of PI-3K/Akt. RT-PCR and quantitative Real-time PCR was performed using gingival mRNAs from periodontitis patients. Immunohistochemistry was performed to analyze the expression and subcellular localization of SDF-1α and CXCR4, together with NF-kβ phosphorylation, in specimens from patients with periodontitis and in an experimental rat periodontitis model.
  
  
  RESULTS
  We found that P. gingivalis LPS up-regulated SDF-1α and CXCR4 protein levels and elevated phosphorylation of the SDF-1α-responsive NF-kβ and Akt at 24 h in HGF-1 cells. SDF-1α and CXCR4 mRNA and protein expression levels were high in all patients with periodontitis. In the P. gingivalis-induced rat experimental periodontitis model, SDF-1α and CXCR4 immunoreactivity was higher in gingival and periodontal ligament tissues compared to the control.
  
  
  CONCLUSIONS
  Our data showed that PI-3K/Akt is an upstream participant in the P. gingivalis LPS-mediated induction of SDF-1α. Taken together, these results suggest that the chemokine SDF-1α and its receptor CXCR4 contribute to P. gingivalis-induced periodontal inflammation.
authors.affiliation: Department of Periodontics and Oral Mucosa Disease, Dalian Stomatological Hospital, 935 Changjiang Road, Shahekou District, Dalian, 116021, China. sunjiang_japan@163.com.|Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan. sunjiang_japan@163.com.
authors.forename: Jiang
authors.identifier: http://orcid.org/0000-0002-0373-0899
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Nemoto
authors.affiliation: Liaison Center for Innovative Dentistry, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
authors.forename: Guang
authors.initials: G
authors.lastname: Hong
authors.affiliation: Division of Advanced Prosthetic Dentistry, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D054377:Chemokine CXCL12 / Q000378:metabolism*; D005881:Gingiva / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D016966:Porphyromonas gingivalis; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000378:metabolism*
chemical_list: C515255:CXCL12 protein, human; C575935:CXCL12 protein, rat; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; C486264:Cxcr4 protein, rat; D019718:Receptors, CXCR4
keywords: CXCR4; Fibroblasts; P. gingivalis; Periodontal inflammation; SDF-1α