RGD Reference Report - Neuroprotection of interleukin-6 against NMDA attack and its signal transduction by JAK and MAPK. - Rat Genome Database

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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.
RGD ID: 2306937
Pubmed: PMID:19061939   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neulet.2008.11.051   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process  IDA 2306937 RGD 
negative regulation of neuron apoptotic process  IDA 2306937Cerebellar granule neuronsRGD 
positive regulation of ERK1 and ERK2 cascade  IDA 2306937Phosphorylation of STAT3 and ERK1/2RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il6  (interleukin 6)


Additional Information