title: Interleukin-6 prevents NMDA-induced neuronal Ca2+ overload via suppression of IP3 receptors.
abstract: OBJECTIVE
  The mechanism underlying interleukin-6 (IL-6) prevention of N-methyl-D-aspartate (NMDA)-induced neuronal Ca(2+) overload was explored at the profile of Ca(2+) channel receptors, including NMDA, inositol 1,4,5-trisphosphate and ryanodine receptors (NMDAR, IP3R and RyR, respectively).
  
  
  METHODS
  Cerebellar granule neurons from 8-day-old rats were exposed to IL-6 (40 or 120 ng ml(-1)) for 8 days and stimulated with NMDA (100 μM) for 15 or 30 minutes.
  
  
  RESULTS
  NMDA evoked an acute and sustained enhancement of intracellular Ca(2+) fluorescence intensity in the entire 15-minute NMDA application period. IL-6 prevented the acute and sustained intracellular Ca(2+) elevation triggered by NMDA in a concentration-dependent manner. MK-801, an NMDAR antagonist, completely suppressed NMDA-evoked neuronal Ca(2+) overload in the absence or presence of IL-6. IP3R antagonist 2-APB lessened NMDA-evoked acute and sustained cytosolic Ca(2+) overload and IL-6 further reduced the acute 2-APB-dependent Ca(2+) component. Dissimilarly, after RyR antagonist DAN treatment, NMDA still induced an acute and sustained elevation of intracellular Ca(2+) levels, and the elevated Ca(2+) was significantly suppressed by IL-6. Moreover, IL-6 down-regulated NMDAR1 and IP3R1 but did not alter RyR2 expression.
  
  
  CONCLUSIONS
  The present results suggest that IL-6 suppresses NMDA-induced neuronal Ca(2+) overload by inhibiting NMDAR and IP3R activities.
authors.affiliation: School of Biological & Basic Medical Sciences, Soochow University, Suzhou, PR China.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Liu
authors.forename: Xiao-Xia
authors.initials: XX
authors.lastname: Fang
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Chen
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Qiu
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Peng
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects / Q000473:pathology*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000037:antagonists & inhibitors*; D015850:Interleukin-6 / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
chemical_list: D002118:Calcium; D053496:Inositol 1,4,5-Trisphosphate Receptors; D015850:Interleukin-6; D016202:N-Methylaspartate; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate