Abstract
In this study we showed that in vivo bacterial lipopolysaccharide (LPS) challenge elevated IL-1beta level in the rodent hippocampus. Antagonists of P2X receptors inhibited LPS-induced IL-1beta level with a pharmacological profile similar to that of P2X(7)R and their inhibitory effect was attenuated in the absence of P2X(7)R. In wild-type mice, LPS overexpressed mRNA encoding P2X(4) and P2X(7) receptors in the hippocampus and caused also a remarkable increase in the levels of IL-1beta in the serum. The hippocampal increase of IL-1beta has substantially alleviated when contamination of circulating blood cells was excluded by transcardial perfusion, indicating the peripheral origin of hippocampal IL-1beta elevation. These results point to the key role of the endogenous activation of peripheral P2X(7)R in the level of IL-1beta in rodent hippocampus under systemic bacterial endotoxin challenge.
Copyright 2009 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / analogs & derivatives
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Adenosine Triphosphate / pharmacology
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Analysis of Variance
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Animals
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Cytokines / metabolism
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / pharmacology
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Enzyme-Linked Immunosorbent Assay / methods
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Gene Expression Regulation / drug effects*
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Hippocampus / drug effects*
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Imidazoles / pharmacology
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Interleukin-1beta / metabolism*
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Lipopolysaccharides / pharmacology*
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Purinergic P2 Receptor Antagonists
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Pyridines / pharmacology
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Pyridoxal Phosphate / analogs & derivatives
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Pyridoxal Phosphate / pharmacology
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RNA, Messenger / metabolism
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Rats
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Rats, Wistar
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Receptors, Purinergic P2 / deficiency
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Receptors, Purinergic P2 / genetics
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Receptors, Purinergic P2 / metabolism*
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Receptors, Purinergic P2X7
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Xanthines / pharmacology
Substances
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Cytokines
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Enzyme Inhibitors
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Imidazoles
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Interleukin-1beta
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Lipopolysaccharides
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P2rx7 protein, mouse
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Purinergic P2 Receptor Antagonists
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Pyridines
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RNA, Messenger
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Receptors, Purinergic P2
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Receptors, Purinergic P2X7
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Xanthines
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pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid
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3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate
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Pyridoxal Phosphate
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Adenosine Triphosphate
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1,3-dipropyl-8-cyclopentylxanthine
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SB 203580