Abstract
Microglia activated after brain injury, are a major source of the pro-inflammatory cytokine interleukin-1 (IL-1), which is known to further exacerbate damage. However, the mechanisms that control IL-1 release in acute neuronal injury are unknown and the purpose of this study was to test the hypothesis that neuronal injury induces IL-1beta release from microglial cells. Here we report that lipopolysaccharide (LPS)-activated rat microglia co-cultured with healthy rat neurons express pro-IL-1beta, which in the absence of cell death accumulates in the cells. Treatment of co-cultures with the excitotoxin N-methyl-D-aspartate (NMDA) induced neuronal cell death leading to the appearance of pro-IL-1beta in the culture supernatant. This effect was reversed by the NMDA receptor antagonist MK-801, and was neuron-dependent, since NMDA had no effect on cell death or pro-IL-1beta release in mixed glial cell cultures. In addition, we show that pro-IL-1beta release from LPS-treated mixed glia or LPS-treated microglia is significantly reduced in the presence of conditioned medium from healthy co-cultures or neuronal cultures respectively. These results demonstrate that injured neurons promote the release of pro-IL-1beta from microglia, possibly...Continue Reading
References
Apr 30, 1992·Nature·N A ThornberryJ Aunins
Jun 1, 1980·The Journal of Cell Biology·K D McCarthy, J de Vellis
Jul 25, 1996·Biochemical and Biophysical Research Communications·Y ImaiS Kohsaka
May 20, 1998·Proceedings of the National Academy of Sciences of the United States of America·H NeumannH Wekerle
Sep 15, 2001·The European Journal of Neuroscience·N ChauvetJ Lestage
Nov 14, 2001·The Journal of Biological Chemistry·Rosalind A Le FeuvreNancy J Rothwell
Feb 28, 2002·Molecular and Cellular Neurosciences·David BroughNancy J Rothwell
Jun 11, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jeffrey M LabasiChristopher A Gabel
Aug 2, 2002·European Journal of Pharmacology·Rosalind Le FeuvreNancy Rothwell
Mar 7, 2003·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Rosalind A Le FeuvreNancy J Rothwell
Mar 22, 2005·Pain·Iain P ChessellGary N Buell
Jul 22, 2005·Nature Reviews. Immunology·Stuart M AllanNancy J Rothwell
Apr 21, 2006·Journal of Neuroscience Research·Randolph N ChristensenMichael S Beattie
May 30, 2006·Nature Neuroscience·Astrid E CardonaRichard M Ransohoff
Jun 30, 2006·Journal of Neurochemistry·Peter ThorntonNancy J Rothwell
Dec 21, 2006·Nature Reviews. Neuroscience·Michelle L BlockJau-Shyong Hong
Apr 13, 2007·Neuropharmacology·Anastasia SimiDavid Brough
Apr 19, 2007·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Adam DenesStuart M Allan
Apr 20, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Barry W McCollStuart M Allan
May 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Pablo PelegrinAnnmarie Surprenant
Citations
Jan 1, 2012·Sleep Disorders·Mak Adam Daulatzai
May 31, 2012·Journal of Neuroinflammation·Tao PangJuan M Saavedra
Mar 18, 2016·Molecular Neurobiology·José IglesiasGeorge E Barreto
Jul 24, 2012·European Journal of Pharmacology·Michael J SeminerioRae R Matsumoto
Mar 31, 2015·Frontiers in Cellular Neuroscience·Karlijn J DoornAnne-Marie van Dam
May 9, 2009·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·H R BoumaT A Schuurs
Mar 25, 2021·Fluids and Barriers of the CNS·María Del Mar Fernández-ArjonaJesús M Grondona