Regulation of interleukin-1β by the interleukin-1 receptor antagonist in the glutamate-injured spinal cord: Endogenous neuroprotection
| Autor: | Zaiming Sam Ye, Guo-Ying Xu, Claire E. Hulsebosch, Song Liu, Clement Echetebu, David J. McAdoo, Kathia M. Johnson |
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| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.drug_class Interleukin-1beta Neurotoxins Excitotoxicity Down-Regulation Glutamic Acid Pharmacology Biology medicine.disease_cause Neuroprotection Rats Sprague-Dawley chemistry.chemical_compound Glutamatergic Excitatory Amino Acid Agonists medicine Animals Molecular Biology Spinal cord injury Gait Disorders Neurologic Spinal Cord Injuries General Neuroscience Glutamate receptor Receptors Interleukin-1 Recovery of Function Receptor antagonist medicine.disease Rats Up-Regulation Disease Models Animal Interleukin 1 Receptor Antagonist Protein Neuroprotective Agents chemistry Cytoprotection Immunology NMDA receptor NBQX Neurology (clinical) Excitatory Amino Acid Antagonists Developmental Biology |
| Zdroj: | Brain Research. 1231:63-74 |
| ISSN: | 0006-8993 |
| DOI: | 10.1016/j.brainres.2008.07.035 |
| Popis: | Elevation of extracellular glutamate contributes to cell death and functional impairments generated by spinal cord injury (SCI), in part through the activation of the neurotoxic cytokine interleukin-1beta (IL-1beta). This study examines the participation of IL-1beta and its regulation by the endogenous interleukin-1 receptor antagonist (IL-1ra) in glutamate toxicity following SCI. Glutamate, glutamatergic agonists and SCI had similar effects on levels of IL-1beta and IL-1ra. Following spinal cord contusion or exposure to elevated glutamate, concentrations of IL-1beta first increased as IL-1ra decreased, and both then changed in the opposite directions. Applying the glutamate agonists NMDA and S-AMPA to the spinal cord caused changes in IL-1beta and IL-1ra levels very similar to those produced by contusion and glutamate. The glutamate antagonists MK801 and NBQX blocked the glutamate-induced changes in IL-1beta and IL-1ra levels. Administering IL-1beta elevated IL-1ra, and administering IL-1ra depressed IL-1beta levels. Infusing IL-beta into the spinal cord impaired locomotion, and infusing IL-1ra improved recovery from glutamate-induced motor impairments. We hypothesize that elevating IL-1ra opposes the damage caused by IL-1beta in SCI by reducing IL-1beta levels as well as by blocking binding of IL-1beta to its receptor. Our results demonstrate that IL-1beta contributes to glutamate damage following SCI; blocking IL-1beta may usefully counteract glutamate toxicity. |
| Databáze: | OpenAIRE |
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