title: The expression and regulation of matrix metalloproteinase-3 is critically modulated by Porphyromonas gingivalis lipopolysaccharide with heterogeneous lipid A structures in human gingival fibroblasts.
abstract: BACKGROUND
  Porphyromonas gingivalis lipopolysaccharide (LPS) is a crucial virulence factor strongly associated with chronic periodontitis which is the primary cause of tooth loss in adults. It exhibits remarkable heterogeneity containing tetra-(LPS(1435/1449)) and penta-(LPS(1690)) acylated lipid A structures. Human gingival fibroblasts (HGFs) as the main resident cells of human gingiva play a key role in regulating matrix metalloproteinases (MMPs) and contribute to periodontal homeostasis. This study investigated the expression and regulation of MMPs1-3 and tissue inhibitors of MMP-1 (TIMP-1) in HGFs in response to P. gingivalis LPS(1435/1449) and LPS(1690) and hexa-acylated E. coli LPS as a reference. The expression of MMPs 1-3 and TIMP-1 was evaluated by real-time PCR and ELISA.
  
  
  RESULTS
  The MMP-3 mRNA and protein were highly upregulated in P. gingivalis LPS(1690)- and E. coli LPS-treated cells, whereas no induction was observed in P. gingivalis LPS(1435/1449)-treated cells. On the contrary, the expression of MMP-1 and -2 was not significantly affected by P. gingivalis LPS lipid A heterogeneity. The TIMP-1 mRNA was upregulated in P. gingivalis LPS(1435/1449)- and E. coli LPS-treated cells. Next, signal transduction pathways involved in P. gingivalis LPS-induced expression of MMP-3 were examined by blocking assays. Blockage of p38 MAPK and ERK significantly inhibited P. gingivalis LPS(1690)-induced MMP-3 expression in HGFs.
  
  
  CONCLUSIONS
  The present findings suggest that the heterogeneous lipid A structures of P. gingivalis LPS differentially modulate the expression of MMP-3 in HGFs, which may play a role in periodontal pathogenesis.
authors.affiliation: Faculty of Dentistry, Periodontology, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Thanuja D K
authors.initials: TD
authors.lastname: Herath
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Chaminda J
authors.initials: CJ
authors.lastname: Seneviratne
authors.forename: Richard P
authors.initials: RP
authors.lastname: Darveau
authors.forename: Cun-Yu
authors.initials: CY
authors.lastname: Wang
authors.forename: Lijian
authors.initials: L
authors.lastname: Jin
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000378:metabolism* / Q000382:microbiology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry / Q000633:toxicity*; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis*; D016966:Porphyromonas gingivalis / Q000472:pathogenicity*; D060888:Real-Time Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D037521:Virulence Factors / Q000737:chemistry / Q000633:toxicity
chemical_list: D008070:Lipopolysaccharides; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D037521:Virulence Factors; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1
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