PMID- 17437036
OWN - NLM
STAT- MEDLINE
DCOM- 20120820
LR  - 20070417
IS  - 0371-0874 (Print)
IS  - 0371-0874 (Linking)
VI  - 59
IP  - 2
DP  - 2007 Apr 25
TI  - Interleukin-6 protects cerebellar granule neurons from NMDA-induced 
      neurotoxicity.
PG  - 150-6
AB  - Interleukin-6 (IL-6) is an important cytokine that participates in inflammation 
      reaction and cell growth and differentiation in the immune and nervous systems. 
      However, the neuroprotection of IL-6 against N-methyl-D-aspartate (NMDA)-induced 
      neurotoxicity and the related underlying mechanisms are still not identified. In 
      the present study, the cultured cerebellar granule neurons (CGNs) from postnatal 
      (8-day) infant rats were chronically exposed to IL-6 for 8 d, and then NMDA (100 
      micromol/L) was applied to the cultured CGNs for 30 min. 
      Methyl-thiazole-tetrazolium (MTT) assay, terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL) method and confocal laser 
      scanning microscope (CLSM) were used to detect neuronal vitality, apoptosis and 
      dynamic changes of intracellular Ca(2+) levels in the neurons, respectively. 
      Anti-gp130 monoclonal antibody (75 ng/mL) was employed to the cultured CGNs with 
      IL-6 to inhibit IL-6 activity so as to evaluate the role of gp130 (a 130 kDa 
      glucoprotein transducing IL-6 signal) in mediating IL-6 neuroprotection. Western 
      blot was used to measure the expressions of phospho-signal transducer and 
      activator of transcription 3 (STAT3) and phospho-extracellular signal regulated 
      kinase 1/2 (ERK1/2) in the cultured CGNs. The NMDA stimulation of the cultured 
      CGNs without IL-6 pretreatment resulted in a significant reduction of the 
      neuronal vitality, notable enhancement of the neuronal apoptosis and 
      intracellular Ca(2+) overload in the neurons. The NMDA stimulation of the CGNs 
      chronically pretreated with IL-6 caused a remarkable increase in the neuronal 
      vitality, marked suppression of neuronal apoptosis and intracellular Ca(2+) 
      overload in the neurons, compared with that in the control neurons without IL-6 
      pretreatment. Furthermore, anti-gp130 antibody blocked the inhibitory effect of 
      IL-6 on NMDA-induced intracellular Ca(2+) overload in the neurons. The levels of 
      phospho-STAT3 and phospho-ERK1/2 were significantly higher in IL-6-pretreated 
      CGNs than those in IL-6-untreated neurons. The results suggest that chronic IL-6 
      pretreatment of CGNs protects the neurons against NMDA-induced neurotoxicity. The 
      neuroprotective effect of IL-6 is closely related to its suppression of 
      NMDA-induced intracellular Ca(2+) overload and is possibly mediated by 
      gp130/JAK-STAT3 and gp130/RAS-ERK1/2 transduction pathways.
FAU - Wang, Xiao-Chun
AU  - Wang XC
AD  - Department of Physiology, Faculty of Medicine, and Key Laboratory of 
      Neuroregeneration of Jiangsu Province, Nantong University, Nantong, China.
FAU - Qiu, Yi-Hua
AU  - Qiu YH
FAU - Peng, Yu-Ping
AU  - Peng YP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Sheng Li Xue Bao
JT  - Sheng li xue bao : [Acta physiologica Sinica]
JID - 20730130R
RN  - 0 (Interleukin-6)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, rat)
RN  - 6384-92-5 (N-Methylaspartate)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Cells, Cultured
MH  - Cerebellum/cytology/*drug effects/metabolism
MH  - Interleukin-6/*physiology
MH  - MAP Kinase Signaling System
MH  - N-Methylaspartate/antagonists & inhibitors/*toxicity
MH  - Neurons/cytology/*drug effects/metabolism
MH  - *Neuroprotective Agents
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - STAT3 Transcription Factor/metabolism
EDAT- 2007/04/18 09:00
MHDA- 2012/08/21 06:00
CRDT- 2007/04/18 09:00
PHST- 2007/04/18 09:00 [pubmed]
PHST- 2012/08/21 06:00 [medline]
PHST- 2007/04/18 09:00 [entrez]
PST - ppublish
SO  - Sheng Li Xue Bao. 2007 Apr 25;59(2):150-6.