Role of p38 in nitric oxide synthase and cyclooxygenase expression, and nitric oxide and PGE2 synthesis in human gingival fibroblasts stimulated with lipopolysaccharides.
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.
Gutiérrez-Venegas
Gloria
G
Laboratorio de Bioquímica, División de Estudios de Posgrado e Investigación de la Facultad de Odontología. Universidad Nacional Autónoma de México, México, Distrito Federal. gloria@fo.odonto.unam.mx
Maldonado-Frías
Silvia
S
Ontiveros-Granados
Ana
A
Kawasaki-Cárdenas
Perla
P
D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis*; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology*; D005881:Gingiva / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008565:Membrane Proteins; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010766:Phosphorylation / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*
D007093:Imidazoles; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D012333:RNA, Messenger; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone; C093642:SB 203580