Interleukin-6 upregulates neuronal adenosine A1 receptors: implications for neuromodulation and neuroprotection.
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.
Biber
Knut
K
Department of Medical Physiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. k.p.h.biber@med.umcg.nl
Pinto-Duarte
A
A
Wittendorp
M C
MC
Dolga
A M
AM
Fernandes
C C
CC
Von Frijtag Drabbe Künzel
J
J
Keijser
J N
JN
de Vries
R
R
Ijzerman
A P
AP
Ribeiro
J A
JA
Eisel
U
U
Sebastião
A M
AM
Boddeke
H W G M
HW
D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography / Q000379:methods; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000528:radiation effects; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D015850:Interleukin-6 / Q000172:deficiency / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects*; D010433:Pentylenetetrazole / Q000494:pharmacology; D011869:Radioligand Assay / Q000379:methods; D043682:Receptor, Adenosine A1 / Q000235:genetics / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects*
D004791:Enzyme Inhibitors; D018683:Excitatory Amino Acid Agents; D015850:Interleukin-6; D043682:Receptor, Adenosine A1; D010433:Pentylenetetrazole