Abstract
Intestinal inflammatory diseases are mediated by dysregulated immune responses to undefined luminal antigens. Feeding hen egg-white lysozyme to mice expressing a transgenic T-cell receptor that recognizes hen egg-white lysozyme peptide 46-61 resulted in no intestinal pathology; however, simultaneous administration of cyclooxygenase-2 inhibitors and dietary hen egg-white lysozyme resulted in increased proliferation of lamina propria mononuclear cells and crypt epithelial cells, crypt expansion and villus blunting. Lamina propria mononuclear cells produce high levels of cyclooxygenase-2-dependent arachidonic acid metabolites, which act as immunomodulators in the immune response to dietary antigen. These findings establish that cyclooxygenase-2-dependent arachidonic acid metabolites are essential in the development and maintenance of intestinal immune homeostasis.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Arachidonic Acid / metabolism*
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CD4-Positive T-Lymphocytes / immunology
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Cells, Cultured
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Cyclooxygenase 2
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors / pharmacology
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Dinoprostone / biosynthesis
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Enzyme Activation / drug effects
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Enzyme-Linked Immunosorbent Assay
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Immunity, Mucosal / immunology
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Intestinal Mucosa / drug effects
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Intestinal Mucosa / immunology
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Intestine, Small / drug effects
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Intestine, Small / pathology
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Isoenzymes / metabolism*
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Leukocytes, Mononuclear / immunology
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Leukocytes, Mononuclear / metabolism
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Macrophages / immunology
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Macrophages / metabolism
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Mice
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Mice, Transgenic
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Muramidase / immunology*
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Nitrobenzenes / pharmacology
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Prostaglandin-Endoperoxide Synthases / metabolism*
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Spleen / drug effects
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Spleen / immunology
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Spleen / metabolism
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Sulfonamides / pharmacology
Substances
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors
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Isoenzymes
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Nitrobenzenes
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Sulfonamides
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N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
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Arachidonic Acid
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Cyclooxygenase 2
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Prostaglandin-Endoperoxide Synthases
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Muramidase
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Dinoprostone