Acute p38-mediated inhibition of NMDA-induced outward currents in hippocampal CA1 neurons by interleukin-1beta.
Interleukin-1beta (IL-1beta) is a potent pro-inflammatory cytokine that is primarily produced by microglia in the brain. IL-1beta inhibits N-methyl-d-aspartate (NMDA)-induced outward currents (I(NMDA-OUT)) through IL-1 type I receptor (IL-1RI) in hippocampal CA1 neurons (Zhang, R., Yamada, J., Hayashi, Y., Wu, Z, Koyama, S., Nakanishi, H., 2008. Inhibition of NMDA-induced outward currents by interleukin-1beta in hippocampal neurons, Biochem. Biophys. Res. Commun. 372, 816-820). Although IL-1RI is associated with mitogen-activated protein kinases, their involvement in the effect of IL-1beta on I(NMDA-OUT) remains unclear. In the present study, we demonstrate that IL-1beta caused activation of p38 mitogen-activated protein kinase and that the p38 inhibitor SB203580 significantly blocked the effect of IL-1beta on I(NMDA-OUT) in hippocampal CA1 neurons. Furthermore, the intracellular perfusion of active recombinant p38alpha significantly decreased the mean amplitude of I(NMDA-OUT). In neurons prepared from inflamed hippocampus, the mean amplitude of I(NMDA-OUT) was significantly reduced. In the inflamed hippocampus, IL-1beta and IL-1RI were expressed mainly in microglia and neurons, respectively. These results suggest that IL-1beta increases the excitability of hippocampal CA1 neurons in the p38-dependent inhibition of I(NMDA-OUT).
Zhang
Ruoyu
R
Department of Aging Science and Pharmacology, Faculty of Dental Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Sun
Li
L
Hayashi
Yoshinori
Y
Liu
Xia
X
Koyama
Susumu
S
Wu
Zhou
Z
Nakanishi
Hiroshi
H
D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000378:metabolism* / Q000503:physiopathology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000378:metabolism* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism* / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D055366:Synaptic Potentials / Q000276:immunology; D009435:Synaptic Transmission / Q000187:drug effects / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D053583:Interleukin-1beta; D017472:Receptors, Interleukin-1; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016202:N-Methylaspartate; D048051:p38 Mitogen-Activated Protein Kinases