IL-4 attenuates the neuroinflammation induced by amyloid-β in vivo and in vitro
Article first published online: 23 JAN 2007
Journal of Neurochemistry
Volume 101, Issue 3, pages 771–781, May 2007
How to Cite
Lyons, A., Griffin, R. J., Costelloe, C. E., Clarke, R. M. and Lynch, M. A. (2007), IL-4 attenuates the neuroinflammation induced by amyloid-β in vivo and in vitro. Journal of Neurochemistry, 101: 771–781. doi: 10.1111/j.1471-4159.2006.04370.x
- Issue published online: 23 JAN 2007
- Article first published online: 23 JAN 2007
- Received May 5, 2006; revised manuscript received October 31, 2006; accepted November 7, 2006.
- Amyloid-β (Aβ);
- interleukin-1β (IL-1β);
- interleukin-4 (IL-4);
- Long-term potentiation (LTP);
- microglial activation;
It has been shown that Aβ inhibits long-term potentiation (LTP) in the rat hippocampus and this is accompanied by an increase in hippocampal concentration of IL-1β. Aβ also increases microglial activation, which is the likely cell source of IL-1β. Because IL-4 attenuates the effects of IL-1β in hippocampus, and microglial activation is inhibited by minocycline, we assessed the ability of both IL-4 and minocycline to modulate the effects of Aβ on LTP and IL-1β concentration. Following treatment with Aβ, IL-4 or minocycline, rats were assessed for their ability to sustain LTP in perforant path-granule cell synapses. We report that the Aβ-induced inhibition of LTP was associated with increases in expression of MHCII, JNK phosphorylation and IL-1β concentration, and that these changes were attenuated by treatment of rats with IL-4 and minocycline. We also report that Aβ-induced increases in expression of MHCII and IL-1β were similarly attenuated by IL-4 and minocycline in glial cultures prepared from neonatal rats. These data suggest that glial cell activation and the consequent increase in IL-1β concentration mediate the inhibitory effect of Aβ on LTP and indicate that IL-4, by down-regulating glial cell activation, antagonizes the effects of Aβ.