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Neuroprotection of interleukin-6 against NMDA attack and its signal transduction by JAK and MAPK.

Authors: Wang, XQ  Peng, YP  Lu, JH  Cao, BB  Qiu, YH 
Citation: Wang XQ, etal., Neurosci Lett. 2009 Jan 30;450(2):122-6. Epub 2008 Nov 27.
Pubmed: (View Article at PubMed) PMID:19061939
DOI: Full-text: DOI:10.1016/j.neulet.2008.11.051

Cytokine interleukin-6 (IL-6) has been well shown to be elevated in brain injury and diseases. However, the significance of IL-6 production in such neuropathologic states remains controversial, and the intracellular signal-transduction pathways involved in the brain IL-6 action are primarily unclear. We previously indicated that exogenous IL-6 protected neurons against glutamate and N-methyl-d-aspartate (NMDA) attacks and the effects of IL-6 was blocked by anti-gp130 antibody. Here, we provide further evidence for the IL-6 neuroprotection and show signal molecules transducing the IL-6 message. The cerebellar granule neurons from postnatal 8-day infant rats were exposed to IL-6 for 8 days, and also pretreated chronically with Janus kinase (JAK) inhibitor AG490 and mitogen-activated protein kinase (MAPK) inhibitor PD98059. NMDA stimulated the cultured neurons for 30 min to induce neuronal injury and death. Cell counting kit-8 assay and Western blot were employed to measure neuronal vitality and cleaved caspase-3 expression, respectively. The chronic IL-6 exposure prevented the suppression of the neuronal vitality and the enhancement of the cleaved caspase-3 level induced by NMDA. The neuroprotective effect of IL-6 depended on IL-6 concentration and neuronal damaged degree. IL-6-induced STAT3 phosphorylation was inhibited by AG490 but not by PD98059; and IL-6-induced ERK1/2 activation was blocked by PD98059 but not by AG490. Either AG490 or PD98059 blocked the IL-6 protection against the NMDA-elicited neuronal vitality decrease and caspase-3 activation increase. These findings suggest that IL-6 protects neurons from NMDA-induced excitoxicity and the IL-6 neuroprotection may be transduced by both JAK/STAT3 and RAS/MAPK pathways.

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CRRD Object Information
CRRD ID: 2306937
Created: 2009-05-12
Species: All species
Last Modified: 2009-05-12
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.