Interleukin-6 prevents NMDA-induced neuronal Ca2+ overload via suppression of IP3 receptors. (August 2013)

• Record Type: Journal Article
• Authors: Liu, Zhan; Fang, Xiao-Xia; Chen, Yu-Ping; Qiu, Yi-Hua; Peng, Yu-Ping
• Is Part Of: Brain injury. Volume 27:Number 9(2013)
• Page Start: 1047
• Page End: 1055
• Publication Date: 2013-08
• Subjects: Brain damage -- Periodicals; Brain -- Wounds and injuries -- Periodicals; Brain Injuries -- Periodicals; 617.481
• DOI: 10.3109/02699052.2013.794970
• Languages: English
• ISSNs: 0269-9052

Abstract

<abstract> <title>Abstract</title> <p> <italic>Primary objective</italic>: The mechanism underlying interleukin-6 (IL-6) prevention of N-methyl-D-aspartate (NMDA)-induced neuronal Ca<sup>2+</sup> overload was explored at the profile of Ca<sup>2+</sup> channel receptors, including NMDA, inositol 1, 4, 5-trisphosphate and ryanodine receptors (NMDAR, IP3R and RyR, respectively).</p> <p> <italic>Methods</italic>: Cerebellar granule neurons from 8-day-old rats were exposed to IL-6 (40 or 120 ng ml<sup>−1</sup>) for 8 days and stimulated with NMDA (100 μM) for 15 or 30 minutes.</p> <p> <italic>Results</italic>: NMDA evoked an acute and sustained enhancement of intracellular Ca<sup>2+</sup> fluorescence intensity in the entire 15-minute NMDA application period. IL-6 prevented the acute and sustained intracellular Ca<sup>2+</sup> elevation triggered by NMDA in a concentration-dependent manner. MK-801, an NMDAR antagonist, completely suppressed NMDA-evoked neuronal Ca<sup>2+</sup> overload in the absence or presence of IL-6. IP3R antagonist 2-APB lessened NMDA-evoked acute and sustained cytosolic Ca<sup>2+</sup> overload and IL-6 further reduced the acute 2-APB-dependent Ca<sup>2+</sup> component. Dissimilarly, after RyR antagonist DAN treatment, NMDA still induced an acute and sustained elevation of intracellular Ca<sup>2+</sup> levels, and the elevated Ca<sup>2+</sup> was significantly suppressed by IL-6. Moreover, IL-6 down-regulated NMDAR1 and IP3R1 but did not alter RyR2 expression.</p> <p> <italic>Conclusion</italic>: The present results suggest that IL-6 suppresses NMDA-induced neuronal Ca<sup>2+</sup> overload by inhibiting NMDAR and IP3R activities.</p> </abstract>