Mechanisms underlying extracellular ATP-evoked interleukin-6 release in mouse microglial cell line, MG-5
Article first published online: 20 DEC 2001
Journal of Neurochemistry
Volume 78, Issue 6, pages 1339–1349, September 2001
How to Cite
Shigemoto-Mogami, Y., Koizumi, S., Tsuda, M., Ohsawa, K., Kohsaka, S. and Inoue, K. (2001), Mechanisms underlying extracellular ATP-evoked interleukin-6 release in mouse microglial cell line, MG-5. Journal of Neurochemistry, 78: 1339–1349. doi: 10.1046/j.1471-4159.2001.00514.x
- Issue published online: 20 DEC 2001
- Article first published online: 20 DEC 2001
- Received March 2, 2001; revised manuscript received June 26, 2001; accepted June 29, 2001.
- mitogen-activated protein kinase
Microglia play various important roles in the CNS via the synthesis of cytokines. The ATP-evoked production of interleukin-6 (IL-6) and its intracellular signals were examined using a mouse microglial cell line, MG-5. ATP, but not its metabolites, produced IL-6 in a concentration-dependent manner. Although ATP activated two mitogen-activated protein kinases, i.e. p38 and extracellular signal-regulated protein kinase, only p38 was involved in the IL-6 induction. However, the activation of p38 was not sufficient for the IL-6 induction because 2′- and 3′-O-(4-benzoylbenzoyl) ATP, an agonist to P2X7 receptors, failed to produce IL-6 despite the fact that it activated p38. Unlike in other cytokines in microglial cells, P2Y rather than P2X7 receptors seem to have a major role in the IL-6 production by the cells. The ATP-evoked IL-6 production was attenuated by Gö6976, an inhibitor of Ca2+-dependent protein kinase C (PKC). The P2Y receptor responsible for these responses was insensitive to pertussis toxin (PTX) and was linked to phospholipase C. Taken together, ATP acting on PTX-insensitive P2Y receptors activates p38 and Ca2+-dependent PKC, thereby resulting in the mRNA expression and release of IL-6 in MG-5. This is a novel pathway for the induction of cytokines in microglia.