title: Effects of nicotine and lipopolysaccharide on the expression of matrix metalloproteinases, plasminogen activators, and their inhibitors in human osteoblasts.
abstract: OBJECTIVE
  Lipopolysaccharide (LPS) from periodontopathic bacteria can initiate alveolar bone loss through the induction of host-derived cytokines. Smoking increases the risk and severity of periodontitis. We examined the effects of nicotine and LPS on the expression of matrix metalloproteinases (MMPs), plasminogen activators (PAs), and their inhibitors, including tissue inhibitors of metalloproteinases (TIMPs) and PA inhibitor-1 (PAI-1), in osteoblasts.
  
  
  METHODS
  The cells were cultured with or without 10(-4) M nicotine and 100 ng/ml LPS for 12 days or with 100 microg/ml polymyxin B, 10(-4) M D-tubocurarine, 10 micromol/ml NS398, or 10(-6) M celecoxib in the presence of either nicotine or LPS for 12 days. The gene and protein expression levels for MMPs, PAs, TIMPs, and PAI-1 were examined using real-time PCR and ELISAs, respectively. PGE(2) production was determined using an ELISA.
  
  
  RESULTS
  The addition of nicotine and/or LPS to the culture medium increased the expression of MMP-1, -2, and -3 and tissue-type PA (tPA); decreased the expression of TIMP-1, -3, and -4; and did not affect expression of TIMP-2 or PAI-1. In the presence of d-tubocurarine or polymyxin B, neither nicotine nor LPS stimulated the expression of MMP-1. In the presence of NS398 or celecoxib, the stimulatory effects of nicotine and LPS on MMP-1 expression were unchanged, but they were unable to stimulate PGE(2) production.
  
  
  CONCLUSIONS
  These results suggest that nicotine and LPS stimulate the resorption process that occurs during turnover of osteoid by increasing the production of MMPs and tPA and by decreasing the production of TIMPs. Furthermore, they suggest that the stimulatory effect of nicotine and LPS on PGE(2) production is independent of their stimulatory effect on MMP-1 expression.
authors.affiliation: Nihon University Graduate School of Dentistry, 1-8-13, Kanda Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Katono
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kawato
authors.forename: Natsuko
authors.initials: N
authors.lastname: Tanabe
authors.forename: Hideki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Naoto
authors.initials: N
authors.lastname: Suzuki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kitami
authors.forename: Toyoko
authors.initials: T
authors.lastname: Morita
authors.forename: Masafumi
authors.initials: M
authors.lastname: Motohashi
authors.forename: Masao
authors.initials: M
authors.lastname: Maeno
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000068579:Celecoxib; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009578:Nitrobenzenes / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010960:Plasminogen Activators / Q000235:genetics / Q000378:metabolism*; D015849:Plasminogen Inactivators / Q000235:genetics / Q000378:metabolism; D011112:Polymyxin B / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D014403:Tubocurarine / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D008070:Lipopolysaccharides; D018733:Nicotinic Antagonists; D009578:Nitrobenzenes; D015849:Plasminogen Inactivators; D011720:Pyrazoles; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D009538:Nicotine; D011451:Prostaglandin-Endoperoxide Synthases; D000469:Alkaline Phosphatase; D010960:Plasminogen Activators; D020782:Matrix Metalloproteinases; D020781:Matrix Metalloproteinase 1; D011112:Polymyxin B; D000068579:Celecoxib; D015232:Dinoprostone; D014403:Tubocurarine