Abstract
The proinflammatory cytokines TNF-alpha, IL-1beta, and IL-6 rise during neuronal damage and activate the apoptotic mitogen-activated protein kinase p38. We studied apoptosis, the levels of TNF-alpha, IL-1beta, and IL-6, and the cell type producing TNF-alpha in rats at 8, 10, and 14 days of age after neonatal exposure to glutamate, which induces neuronal damage. TNF-alpha production was significantly increased by glutamate, but inhibited by SB203580 (a p38 inhibitor). TNF-alpha, IL-1beta, and IL-6 mRNA levels increased, but SB203580 did not modify their expression. Thus, the p38 signaling pathway influences the expression of inflammatory genes and its inhibition may offer anti-inflammatory therapy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Apoptosis / drug effects
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Apoptosis / immunology*
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Cytokines / biosynthesis
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Cytokines / metabolism*
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Cytokines / physiology
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Hippocampus / enzymology*
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Hippocampus / immunology
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Hippocampus / metabolism
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Hippocampus / pathology*
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Imidazoles / administration & dosage
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Inflammation Mediators / metabolism*
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Inflammation Mediators / physiology
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Injections, Subcutaneous
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Interleukin-1 / biosynthesis
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Interleukin-1 / genetics
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Interleukin-6 / biosynthesis
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Interleukin-6 / genetics
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Neuroglia / immunology
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Neuroglia / metabolism
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Neuroglia / pathology
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Neurons / immunology
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Neurons / metabolism
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Neurons / pathology
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Pyridines / administration & dosage
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Rats, Wistar
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Signal Transduction / drug effects
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Signal Transduction / immunology
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Sodium Glutamate / administration & dosage
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Sodium Glutamate / toxicity*
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / 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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Cytokines
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Imidazoles
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Inflammation Mediators
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Interleukin-1
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Interleukin-6
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Pyridines
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RNA, Messenger
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Tumor Necrosis Factor-alpha
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p38 Mitogen-Activated Protein Kinases
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SB 203580
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Sodium Glutamate