Abstract
The immunological response in the brain is crucial to overcome neuropathological events. Some inflammatory mediators, such as the immunoregulatory cytokine interleukin-6 (IL-6) affect neuromodulation and may also play protective roles against various noxious conditions. However, the fundamental mechanisms underlying the long-term effects of IL-6 in the brain remain unclear. We now report that IL-6 increases the expression and function of the neuronal adenosine A1 receptor, with relevant consequences to synaptic transmission and neuroprotection. IL-6-induced amplification of A1 receptor function enhances the responses to readily released adenosine during hypoxia, enables neuronal rescue from glutamate-induced death, and protects animals from chemically induced convulsing seizures. Taken together, these results suggest that IL-6 minimizes the consequences of excitotoxic episodes on brain function through the enhancement of endogenous adenosinergic signaling.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Analysis of Variance
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Animals
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Autoradiography / methods
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Cell Survival / drug effects
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Cells, Cultured
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Cerebral Cortex / cytology
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Embryo, Mammalian
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Enzyme Inhibitors / pharmacology
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Excitatory Amino Acid Agents / pharmacology
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / radiation effects
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Hippocampus / drug effects
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Hippocampus / physiology
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Interleukin-6 / deficiency
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Interleukin-6 / 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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Neurons / drug effects*
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Pentylenetetrazole / pharmacology
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Radioligand Assay / methods
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Receptor, Adenosine A1 / genetics
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Receptor, Adenosine A1 / metabolism*
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Seizures / chemically induced
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Seizures / drug therapy
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Seizures / genetics
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Synaptic Transmission / drug effects*
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Time Factors
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Up-Regulation / drug effects*
Substances
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Enzyme Inhibitors
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Excitatory Amino Acid Agents
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Interleukin-6
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Receptor, Adenosine A1
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Pentylenetetrazole