title: Substance P regulates the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinase in cultured human gingival fibroblasts.
abstract: OBJECTIVE
  Substance P may play a role in the pathogenesis of periodontal disease; however, its mechanisms of modulation are not clear. This study evaluated the effect of two concentrations of Substance P on the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in cultured human gingival fibroblasts.
  
  
  METHODS
  Fibroblasts were stimulated for 48 h with 10(-4) or 10(-9) m Substance P; untreated fibroblasts served as controls. The expression of MMP-1, -2, -3, -7 and -11 and of TIMP-1 and -2 was evaluated using real-time polymerase chain reaction and western blotting.
  
  
  RESULTS
  There was a significant, concentration-dependent stimulatory effect of Substance P on MMP-1, -2, -3 and -7 and TIMP-2 gene expression (p < 0.05), and a probable effect on MMP-11 (p = 0.06). At the higher concentration (10(-4) m Substance P), MMP-1, -2, -3, -7 and -11 and TIMP-2 showed the greatest up-regulation; at the lower concentration (10(-9) m Substance P), MMP-1, -3 and -7 and TIMP-2 exhibited diminished up-regulation, with MMP-2 and -11 showing down-regulation (p < 0.05). Expression of TIMP-1 was not affected by Substance P (p > 0.05). Western blotting confirmed that Substance P up-regulated MMP-1, -2, -3 and -11 and TIMP-2. MMP-1, -3 and -11 and TIMP-2 showed greater up-regulation at the higher Substance P concentration and diminished up-regulation at the lower concentration. MMP-2 was up-regulated to a similar degree at both Substance P concentrations.
  
  
  CONCLUSIONS
  In gingival fibroblast cells, Substance P at the higher concentration (10(-4) m) induced greater up-regulation of MMP-1, -3 and -11 and TIMP-2 expression, but at the lower concentration (10(-9) m) induced diminished up-regulation, which may represent a mechanism for modulating periodontal breakdown.
authors.affiliation: Department of Oral Pathology, University of São Paulo, School of Dentistry, Brazil. patriciacury@slmandic.com.br
authors.forename: P R
authors.initials: PR
authors.lastname: Cury
authors.forename: F
authors.initials: F
authors.lastname: Canavez
authors.forename: V C
authors.initials: VC
authors.lastname: de Araújo
authors.forename: C
authors.initials: C
authors.lastname: Furuse
authors.forename: N S
authors.initials: NS
authors.lastname: de Araújo
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005347:Fibroblasts / Q000201:enzymology; D015870:Gene Expression; D005881:Gingiva / Q000166:cytology / Q000201:enzymology*; D006801:Humans; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D013373:Substance P / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis*; D015854:Up-Regulation
chemical_list: D019714:Tissue Inhibitor of Metalloproteinases; D013373:Substance P; D020782:Matrix Metalloproteinases