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Cyclooxygenase-2-dependent prostaglandin E2 down-regulates intercellular adhesion molecule-1 expression via EP2/EP4 receptors in interleukin-1beta-stimulated human gingival fibroblasts. 2000

K Noguchi, and K Iwasaki, and M Shitashige, and H Endo, and H Kondo, and I Ishikawa
Periodontology, Department of Hard Tissue Engineering, Graduate School, Tokyo Medical and Dental University, Japan. kazuyuki-noguchi.peri@dent.tmd.ac.jp

Prostaglandin E2 (PGE2), which exerts its actions via EP receptors (EP1, EP2, EP3, and EP4), is a bioactive metabolite of arachidonic acid produced by cyclooxygenase (COX)-1 and/or COX-2. We have previously demonstrated that PGE2 down-regulates intercellular adhesion molecule-1 (ICAM-1) expression in interleukin-1beta (IL-1beta)-stimulated human gingival fibroblasts (HGF). In the present study, we investigated which COX was involved in down-regulation of ICAM-1 expression by PGE2 in IL-1beta-stimulated HGF and which subtypes of EP receptors modulated the ICAM-1 expression. NS-398, a specific COX-2 inhibitor, completely inhibited PGE2 production by IL-1beta-stimulated HGF, as did indomethacin, a COX-1/COX-2 inhibitor. Northern blot analysis and immunocytochemical staining showed that mRNA and protein of COX-2 were expressed in IL-1beta-challenged HGF, but not in unstimulated HGF, and that the expression of mRNA and protein of COX-1 was similar both in unstimulated and in stimulated cells. NS-398 and indomethacin enhanced ICAM-1 expression in IL-1beta-challenged HGF. EP1, EP2, and EP4 receptor mRNA was expressed in HGF according to reverse-transcription/polymerase chain-reaction. PGE2, 11-deoxy-PGE1 (a selective EP2/EP4 agonist), and Butaprost (a selective EP2 agonist) attenuated IL-1beta-elicited ICAM-1 expression, although Butaprost was less potent than PGE2 and 11-deoxy-PGE1. AH-23848B, an EP4 antagonist, antagonized the inhibitory effect of IL-1beta-elicited ICAM-1 expression by PGE2. Sulprostone, an EP1/EP3 agonist, had no effect on IL-1beta-elicited ICAM-1 expression. Analysis of these data suggests that COX-2-derived PGE2 down-regulates ICAM-1 expression via EP2/EP4 receptors in IL-1beta-stimulated HGF.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D007375 Interleukin-1 A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. IL-1,Lymphocyte-Activating Factor,Epidermal Cell Derived Thymocyte-Activating Factor,Interleukin I,Macrophage Cell Factor,T Helper Factor,Epidermal Cell Derived Thymocyte Activating Factor,Interleukin 1,Lymphocyte Activating Factor
D007527 Isoenzymes Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics. Alloenzyme,Allozyme,Isoenzyme,Isozyme,Isozymes,Alloenzymes,Allozymes
D008565 Membrane Proteins Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D011451 Prostaglandin-Endoperoxide Synthases Enzyme complexes that catalyze the formation of PROSTAGLANDINS from the appropriate unsaturated FATTY ACIDS, molecular OXYGEN, and a reduced acceptor. Fatty Acid Cyclo-Oxygenase,PGH Synthase,Prostaglandin H Synthase,Prostaglandin Synthase,Prostaglandin-Endoperoxide Synthase,Arachidonic Acid Cyclooxygenase,Cyclo-Oxygenase,Cyclooxygenase,Cyclooxygenases,Hydroperoxide Cyclase,PGH2 Synthetase,Prostaglandin Cyclo-Oxygenase,Prostaglandin Cyclooxygenase,Prostaglandin Endoperoxide Synthetase,Prostaglandin G-H Synthase,Prostaglandin H2 Synthetase,Prostaglandin Synthetase,Cyclase, Hydroperoxide,Cyclo Oxygenase,Cyclo-Oxygenase, Fatty Acid,Cyclo-Oxygenase, Prostaglandin,Cyclooxygenase, Arachidonic Acid,Cyclooxygenase, Prostaglandin,Endoperoxide Synthetase, Prostaglandin,Fatty Acid Cyclo Oxygenase,G-H Synthase, Prostaglandin,Prostaglandin Cyclo Oxygenase,Prostaglandin Endoperoxide Synthases,Prostaglandin G H Synthase,Synthase, PGH,Synthase, Prostaglandin,Synthase, Prostaglandin G-H,Synthase, Prostaglandin H,Synthase, Prostaglandin-Endoperoxide,Synthases, Prostaglandin-Endoperoxide,Synthetase, PGH2,Synthetase, Prostaglandin,Synthetase, Prostaglandin Endoperoxide,Synthetase, Prostaglandin H2
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D005881 Gingiva Oral tissue surrounding and attached to TEETH. Gums,Interdental Papilla,Papilla, Interdental,Gum
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000704 Analysis of Variance A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable. ANOVA,Analysis, Variance,Variance Analysis,Analyses, Variance,Variance Analyses

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