title: Reduction in lipopolysaccharide-induced apoptosis of fibroblasts obtained from a patient with gingival overgrowth during nifedipine-treatment.
abstract: OBJECTIVE
  We have previously demonstrated that the mechanism of nifedipine (NIF)-induced gingival overgrowth is related to the observation that proliferation and cell cycle progression of gingival fibroblasts derived from NIF reactive patient (NIFr) are greater than those from NIF non-reactive patient (NIFn). Gingival overgrowth has also been reported to be a result of inhibited apoptosis of gingival fibroblasts. Apoptosis in fibroblasts is induced by lipopolysaccharide (LPS). Thus, we focused upon evaluating whether there is a difference in LPS-induced apoptosis between NIFn and NIFr.
  
  
  METHODS
  Both NIFn and NIFr were arrested in DMEM containing 0.5% FBS, stimulated by LPS, and assayed for apoptosis, cell cycle analysis, Western blotting, and caspase activity.
  
  
  RESULTS
  Compared to NIFn, the number of apoptotic cells was significantly decreased and the percentage of cells in S and G(2)/M phase was significantly increased in NIFr. The levels of Bax and cytochrome c proteins in NIFr were not up-regulated by LPS compared with NIFn. Both NIFn and NIFr displayed the following changes in protein expression: increased Bad, decreased Bcl-xL, and unchanged Bcl-2 and p53. Caspase-3 and -9 activities were significantly increased by LPS in NIFn but were unchanged in NIFr. Caspase-2 activity remained constant whilst caspase-8 activity significantly increased upon LPS treatment in both NIFn and NIFr.
  
  
  CONCLUSIONS
  Bad, Bax, cytochrome c, p53, and caspases-2, -3, -8, and -9 are pro-apoptotic proteins. Bcl-2 and Bcl-xL are anti-apoptotic proteins. Thus, the mechanism of NIF-induced gingival overgrowth might be related to decreased apoptosis in NIFr through a reduction of Bax, cytochrome c, and caspase-3 and -9.
authors.affiliation: Department of Oral Molecular Pharmacology, Nihon University School of Dentistry at Matsudo, 2-870-1 Sakaecho-Nishi, Matsudo, Chiba 271-8587, Japan. takeuchi.reiri@nihon-u.ac.jp
authors.forename: Reiri
authors.initials: R
authors.lastname: Takeuchi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Akimoto
authors.forename: Akira
authors.initials: A
authors.lastname: Fujii
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053143:Caspase 2 / Q000032:analysis / Q000187:drug effects; D053148:Caspase 3 / Q000032:analysis / Q000187:drug effects; D053181:Caspase 8 / Q000032:analysis / Q000187:drug effects; D053453:Caspase 9 / Q000032:analysis / Q000187:drug effects; D018929:Cell Culture Techniques; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003546:Cysteine Endopeptidases / Q000032:analysis / Q000187:drug effects; D045304:Cytochromes c / Q000032:analysis / Q000187:drug effects; D004926:Escherichia coli; D005347:Fibroblasts / Q000187:drug effects*; D016195:G2 Phase / Q000187:drug effects; D005881:Gingiva / Q000187:drug effects* / Q000473:pathology; D019214:Gingival Overgrowth / Q000139:chemically induced / Q000473:pathology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008677:Metaphase / Q000187:drug effects; D009543:Nifedipine / Q000009:adverse effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000187:drug effects; D016196:S Phase / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000187:drug effects; D014665:Vasodilator Agents / Q000009:adverse effects*; D051028:bcl-2-Associated X Protein / Q000032:analysis / Q000187:drug effects; D051025:bcl-Associated Death Protein / Q000032:analysis / Q000187:drug effects; D051020:bcl-X Protein / Q000032:analysis / Q000187:drug effects
chemical_list: C494819:BAD protein, human; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D008070:Lipopolysaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D014665:Vasodilator Agents; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein; D045304:Cytochromes c; C490360:CASP2 protein, human; C505530:CASP8 protein, human; D053143:Caspase 2; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D003546:Cysteine Endopeptidases; D009543:Nifedipine