Abstract
Periodontal disease, a gingival inflammatory disease caused by gram-negative bacteria, is the main cause of tooth loss. Lipopolysaccharides (LPS) present in bacterial cell walls induce human gingival fibroblasts' production of pro-inflammatory cytotoxins such as IL-1beta and TNFalpha. The goal of this study was to determine p38 role in the expression of inducible nitric oxide synthase enzyme (i-NOS) and cyclooxygenase (COX-2), as well as in PGE(2) and nitric oxide synthesis in human gingival fibroblasts challenged with LPS. We found that lipopolysaccharides induced a rapid and significant increase in p38 phosphorylation. After interruption of p38 transduction pathway by pre-treatment with inhibitor SB203580, no response to stimulation with LPS was observed; i-NOS expression and nitric oxide synthesis was completely blocked. However, p38 inhibition only partially blocked COX-2 expression and PGE2 synthesis. We conclude that p38 is critically involved in i-NOS induction, and that it participates in COX-2 expression and in PGE2 synthesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cells, Cultured
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Cyclooxygenase 2
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Dinoprostone / biosynthesis*
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Fibroblasts / drug effects
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Fibroblasts / enzymology*
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Gingiva / cytology*
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Gingiva / drug effects
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Humans
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Imidazoles / pharmacology
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Lipopolysaccharides / pharmacology
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Membrane Proteins
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Nitric Oxide / biosynthesis
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Nitric Oxide Synthase / genetics
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Nitric Oxide Synthase / metabolism*
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Nitric Oxide Synthase Type II
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Phosphorylation / drug effects
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Prostaglandin-Endoperoxide Synthases / genetics
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Prostaglandin-Endoperoxide Synthases / metabolism*
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Protein Kinase Inhibitors / pharmacology
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Pyridines / pharmacology
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RNA, Messenger / analysis
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RNA, Messenger / metabolism
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
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p38 Mitogen-Activated Protein Kinases / metabolism
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p38 Mitogen-Activated Protein Kinases / physiology*
Substances
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Imidazoles
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Lipopolysaccharides
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Membrane Proteins
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Protein Kinase Inhibitors
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Pyridines
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RNA, Messenger
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Nitric Oxide
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NOS2 protein, human
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Cyclooxygenase 2
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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p38 Mitogen-Activated Protein Kinases
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Dinoprostone
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SB 203580