Expression of interleukin-1 receptors and their role in interleukin-1 actions in murine microglial cells
Article first published online: 4 NOV 2002
Journal of Neurochemistry
Volume 83, Issue 4, pages 754–763, November 2002
How to Cite
Pinteaux, E., Parker, L. C., Rothwell, N. J. and Luheshi, G. N. (2002), Expression of interleukin-1 receptors and their role in interleukin-1 actions in murine microglial cells. Journal of Neurochemistry, 83: 754–763. doi: 10.1046/j.1471-4159.2002.01184.x
- Issue published online: 4 NOV 2002
- Article first published online: 4 NOV 2002
- Received May 9, 2002; revised manuscript received July 26, 2002; accepted August 20, 2002.
- interleukin 1 receptors;
- interleukin 1 signaling;
- microglial cells;
- mitogen-activated protein kinase;
- nuclear factor kappa B
Interleukin (IL)-1 is an important mediator of acute brain injury and inflammation, and has been implicated in chronic neurodegeneration. The main source of IL-1 in the CNS is microglial cells, which have also been suggested as targets for its action. However, no data exist demonstrating expression of IL-1 receptors [IL-1 type-I receptor (IL-1RI), IL-1 type-II receptor (IL-1RII) and IL-1 receptor accessory protein (IL-1RAcP)] on microglia. In the present study we investigated whether microglia express IL-1 receptors and whether they present target or modulatory properties for IL-1 actions. RT–PCR analysis demonstrated lower expression of IL-1RI and higher expression of IL-1RII mRNAs in mouse microglial cultures compared with mixed glial or pure astrocyte cultures. Bacterial lipopolysaccharide (LPS) caused increased expression of IL-1RI, IL-1RII and IL-1RAcP mRNAs, induced the release of IL-1β, IL-6 and prostaglandin-E2 (PGE2), and activated nuclear factor κB (NF-κB) and the mitogen-activated protein kinases (MAPKs) p38, and extracellular signal-regulated protein kinase (ERK1/2), but not c-Jun N-terminal kinase (JNK) in microglial cultures. In comparison, IL-1β induced the release of PGE2, IL-6 and activated NF-κB, p38, JNK and ERK1/2 in mixed glial cultures, but failed to induce any of these responses in microglial cell cultures. IL-1β also failed to affect LPS-primed microglial cells. Interestingly, a neutralizing antibody to IL-1RII significantly increased the concentration of IL-1β in the medium of LPS-treated microglia and exacerbated the IL-1β-induced IL-6 release in mixed glia, providing the first evidence that microglial IL-1RII regulates IL-1β actions by binding excess levels of this cytokine during brain inflammation.