Interleukin-6 upregulates neuronal adenosine A(1) receptors: Implications for neuromodulation and neuroprotection

Knut Biber; A. Pinto-Duarte; M. C. Wittendorp; Amalia Dolga; C.C. Fernandes; J. von Frijtag Drabbe Künzel; Jan N. Keijser; R. de Vries; A. P. IJzerman; J. A. Ribeiro; U. Eisel; A. M. Sebastiao; H. W. G. M. Boddeke

doi:10.1038/sj.npp.1301612

Interleukin-6 upregulates neuronal adenosine A(1) receptors: Implications for neuromodulation and neuroprotection

Knut Biber^*, A. Pinto-Duarte, M. C. Wittendorp, Amalia Dolga, C.C. Fernandes, J. von Frijtag Drabbe Künzel, Jan N. Keijser, R. de Vries, A. P. IJzerman, J. A. Ribeiro, U. Eisel, A. M. Sebastiao, H. W. G. M. Boddeke

^*Corresponding author for this work

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64 Citations (Scopus)

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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 A(1) receptor, with relevant consequences to synaptic transmission and neuroprotection. IL-6-induced amplification of A(1) 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.

Original language	English
Pages (from-to)	2237-2250
Number of pages	14
Journal	Neuropsychopharmacology
Volume	33
Issue number	9
DOIs	https://doi.org/10.1038/sj.npp.1301612
Publication status	Published - Aug-2008

Keywords

brain inflammation
cytokines
excitotoxicity
seizures
hypoxia
adenosine A(1) receptor
CENTRAL-NERVOUS-SYSTEM
INHIBITORY SYNAPTIC TRANSMISSION
DATA-ACQUISITION PROGRAM
RAT HIPPOCAMPUS
MESSENGER-RNA
CEREBROSPINAL-FLUID
INDUCED SEIZURES
MOUSE-BRAIN
EPILEPTIC SEIZURES
CEREBRAL-ISCHEMIA

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1 Erratum

Erratum: Interleukin-6 upregulates neuronal adenosine AI receptors: Implications for neuromodulation and neuroprotection (vol 33, pg 2237, 2008)
Biber, K., Pinto-Duarte, A., Wittendorp, M. C., Dolga, A. M., Fernandes, C. C., von Frijtag Drabbe Künzel, J., Keijser, J. N., de Vries, R., IJzerman, A. P., Ribeiro, J. A., Eisel, U., Sebastiao, A. M. & Boddeke, H. W. G. M., Oct-2008, In: Neuropsychopharmacology. 33, 11, p. 2789 1 p.
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3 Citations (Scopus)

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Biber, K., Pinto-Duarte, A., Wittendorp, M. C., Dolga, A., Fernandes, C. C., Frijtag Drabbe Künzel, J. V., Keijser, J. N., de Vries, R., IJzerman, A. P., Ribeiro, J. A., Eisel, U., Sebastiao, A. M., & Boddeke, H. W. G. M. (2008). Interleukin-6 upregulates neuronal adenosine A(1) receptors: Implications for neuromodulation and neuroprotection. Neuropsychopharmacology, 33(9), 2237-2250. https://doi.org/10.1038/sj.npp.1301612

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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 A(1) receptor, with relevant consequences to synaptic transmission and neuroprotection. IL-6-induced amplification of A(1) 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.",

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author = "Knut Biber and A. Pinto-Duarte and Wittendorp, {M. C.} and Amalia Dolga and C.C. Fernandes and {Frijtag Drabbe K{\"u}nzel}, {J. von} and Keijser, {Jan N.} and {de Vries}, R. and IJzerman, {A. P.} and Ribeiro, {J. A.} and U. Eisel and Sebastiao, {A. M.} and Boddeke, {H. W. G. M.}",

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Biber, K, Pinto-Duarte, A, Wittendorp, MC, Dolga, A, Fernandes, CC, Frijtag Drabbe Künzel, JV, Keijser, JN, de Vries, R, IJzerman, AP, Ribeiro, JA, Eisel, U, Sebastiao, AM & Boddeke, HWGM 2008, 'Interleukin-6 upregulates neuronal adenosine A(1) receptors: Implications for neuromodulation and neuroprotection', Neuropsychopharmacology, vol. 33, no. 9, pp. 2237-2250. https://doi.org/10.1038/sj.npp.1301612

TY - JOUR

T1 - Interleukin-6 upregulates neuronal adenosine A(1) receptors

T2 - Implications for neuromodulation and neuroprotection

AU - Biber, Knut

AU - Pinto-Duarte, A.

AU - Wittendorp, M. C.

AU - Dolga, Amalia

AU - Fernandes, C.C.

AU - Frijtag Drabbe Künzel, J. von

AU - Keijser, Jan N.

AU - de Vries, R.

AU - IJzerman, A. P.

AU - Ribeiro, J. A.

AU - Eisel, U.

AU - Sebastiao, A. M.

AU - Boddeke, H. W. G. M.

PY - 2008/8

Y1 - 2008/8

N2 - 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 A(1) receptor, with relevant consequences to synaptic transmission and neuroprotection. IL-6-induced amplification of A(1) 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.

AB - 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 A(1) receptor, with relevant consequences to synaptic transmission and neuroprotection. IL-6-induced amplification of A(1) 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.

KW - brain inflammation

KW - cytokines

KW - excitotoxicity

KW - seizures

KW - hypoxia

KW - adenosine A(1) receptor

KW - CENTRAL-NERVOUS-SYSTEM

KW - INHIBITORY SYNAPTIC TRANSMISSION

KW - DATA-ACQUISITION PROGRAM

KW - RAT HIPPOCAMPUS

KW - MESSENGER-RNA

KW - CEREBROSPINAL-FLUID

KW - INDUCED SEIZURES

KW - MOUSE-BRAIN

KW - EPILEPTIC SEIZURES

KW - CEREBRAL-ISCHEMIA

U2 - 10.1038/sj.npp.1301612

DO - 10.1038/sj.npp.1301612

M3 - Article

C2 - 17987062

SN - 0893-133X

VL - 33

SP - 2237

EP - 2250

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

IS - 9

ER -

Interleukin-6 upregulates neuronal adenosine A(1) receptors: Implications for neuromodulation and neuroprotection

Abstract

Keywords

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Research output

Erratum: Interleukin-6 upregulates neuronal adenosine AI receptors: Implications for neuromodulation and neuroprotection (vol 33, pg 2237, 2008)

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