Heme oxygenase-1 mediates nicotine- and lipopolysaccharide-induced expression of cyclooxygenase-2 and inducible nitric oxide synthase in human periodontal ligament cells.
OBJECTIVE
Although heme oxygenase-1 (HO-1) plays a key role in inflammation, its anti-inflammatory effects and mechanism of action in periodontitis are still unknown. This study aimed to identify the effects of HO-1 on the proinflammatory mediators activated by nicotine and lipopolysaccharide (LPS) stimulation in human periodontal ligament (PDL) cells.


METHODS
The production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) was evaluated using Griess reagent and an enzyme immunoassay, respectively. The expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and HO-1 proteins was evaluated by Western blot analysis.


RESULTS
Lipopolysaccharide and nicotine synergistically induced the production of NO and PGE(2) and increased the protein expression of iNOS, COX-2 and HO-1. Treatment with an HO-1 inhibitor and HO-1 small interfering RNAs blocked the LPS- and nicotine-stimulated NO and PGE(2) release as well as the expression of iNOS and COX-2.


CONCLUSIONS
Our data suggest that the nicotine- and LPS-induced inflammatory effects on PDL cells may act through a novel mechanism involving the action of HO-1. Thus, HO-1 may provide a potential therapeutic target for the treatment of periodontal disease associated with smoking and dental plaque.
Pi
S-H
SH
Department of Periodontology, Wonkwang University, Iksan, South Korea.
Jeong
G-S
GS
Oh
H-W
HW
Kim
Y-S
YS
Pae
H-O
HO
Chung
H-T
HT
Lee
S-K
SK
Kim
E-C
EC
D000730:Androstadienes / Q000494:pharmacology; D000873:Anthracenes / Q000494:pharmacology; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000187:drug effects*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000032:analysis / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008665:Metalloporphyrins / Q000494:pharmacology; D016328:NF-kappa B / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000032:analysis / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000187:drug effects*; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011524:Protoporphyrins / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D014162:Transfection; D000077191:Wortmannin
D000730:Androstadienes; D000873:Anthracenes; D052246:Cyclooxygenase 2 Inhibitors; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D008665:Metalloporphyrins; D016328:NF-kappa B; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011524:Protoporphyrins; D034741:RNA, Small Interfering; C432165:pyrazolanthrone; D009569:Nitric Oxide; D009538:Nicotine; C032628:tin protoporphyrin IX; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; D048031:JNK Mitogen-Activated Protein Kinases; D015232:Dinoprostone; D000077191:Wortmannin