title: Lipopolysaccharide enhances the production of nicotine-induced prostaglandin E2 by an increase in cyclooxygenase-2 expression in osteoblasts.
abstract: Previous studies have indicated that lipopolysaccharide (LPS) from Gram-negative bacteria in plaque induces the release of prostaglandin E(2) (PGE(2)), which promotes alveolar bone resorption in periodontitis, and that tobacco smoking might be an important risk factor for the development and severity of periodontitis. We determined the effect of nicotine and LPS on alkaline phosphatase (ALPase) activity, PGE(2) production, and the expression of cyclooxygenase (COX-1, COX-2), PGE(2) receptors Ep1>4, and macrophage colony stimulating factor (M-CSF) in human osteoblastic Saos-2 cells. The cells were cultured with 10(-3) M nicotine in the presence of 0, 1, or 10 mug/ml LPS, or with LPS alone. ALPase activity decreased in cells cultured with nicotine or LPS alone, and decreased further in those cultured with both nicotine and LPS, whereas PGE(2) production significantly increased in the former and increased further in the latter. By itself, nicotine did not affect expression of COX-1, COX-2, any of the PGE(2) receptors, or M-CSF, but when both nicotine and LPS were present, expression of COX-2, Ep3, Ep4, and M-CSF increased significantly. Simultaneous addition of 10(-4) M indomethacin eliminated the effects of nicotine and LPS on ALPase activity, PGE(2) production, and M-CSF expression. Phosphorylation of protein kinase A was high in cells cultured with nicotine and LPS. These results suggest that LPS enhances the production of nicotine-induced PGE(2) by an increase in COX-2 expression in osteoblasts, that nicotine-LPS-induced PGE2 interacts with the osteoblast Ep4 receptor primarily in autocrine or paracrine mode, and that the nicotine-LPS-induced PGE(2) then decreases ALPase activity and increases M-CSF expression.
authors.affiliation: Department of Oral Health Sciences, Nihon University School of Dentistry, Tokyo, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Shoji
authors.forename: Natsuko
authors.initials: N
authors.lastname: Tanabe
authors.forename: Narihiro
authors.initials: N
authors.lastname: Mitsui
authors.forename: Naoto
authors.initials: N
authors.lastname: Suzuki
authors.forename: Osamu
authors.initials: O
authors.lastname: Takeichi
authors.forename: Tomoko
authors.initials: T
authors.lastname: Katono
authors.forename: Akira
authors.initials: A
authors.lastname: Morozumi
authors.forename: Masao
authors.initials: M
authors.lastname: Maeno
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D015232:Dinoprostone / Q000096:biosynthesis*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity*; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D009538:Nicotine / Q000633:toxicity*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D018078:Receptors, Prostaglandin E / Q000235:genetics
chemical_list: D017931:DNA Primers; D008070:Lipopolysaccharides; D018078:Receptors, Prostaglandin E; D009538:Nicotine; D016173:Macrophage Colony-Stimulating Factor; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D017868:Cyclic AMP-Dependent Protein Kinases; D000469:Alkaline Phosphatase; D015232:Dinoprostone; D007213:Indomethacin