Unknown

Dataset Information

0

Neuroprotection by interleukin-6 is mediated by signal transducer and activator of transcription 3 and antioxidative signaling in ischemic stroke.


ABSTRACT: Interleukin-6 (IL-6) has been shown to have a neuroprotective effect in brain ischemic injury. However, its molecular mechanisms are still poorly understood. In this study, we investigated the neuroprotective role of the IL-6 receptor (IL-6R) by IL-6 in the reactive oxygen species defense system after transient focal cerebral ischemia (tFCI).IL-6 was injected in mice before and after middle cerebral artery occlusion. Coimmunoprecipitation assays were performed for analysis of an IL-6R association after tFCI. Primary mouse cerebral cortical neurons were transfected with small interfering RNA probes targeted to IL-6R? or gp130 and were used for chromatin-immunoprecipitation assay, luciferase promoter assay, and cell viability assay. Reduction in infarct volumes by IL-6 was measured after tFCI.IL-6R was disrupted through a disassembly between IL-6R? and gp130 associated by protein oxidation after reperfusion after tFCI. This suppressed phosphorylation of signal transducer and activator of transcription 3 (STAT3) and finally induced neuronal cell death through a decrease in manganese-superoxide dismutase. However, IL-6 injections prevented disruption of IL-6R against reperfusion after tFCI, consequently restoring activity of STAT3 through recovery of the binding of STAT3 to gp130. Moreover, IL-6 injections restored the transcriptional activity of the manganese-superoxide dismutase promoter through recovery of the recruitment of STAT3 to the manganese-superoxide dismutase promoter and reduced infarct volume after tFCI.This study demonstrates that IL-6 has a neuroprotective effect against cerebral ischemic injury through IL-6R-mediated STAT3 activation and manganese-superoxide dismutase expression.

SUBMITTER: Jung JE 

PROVIDER: S-EPMC3395465 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

Neuroprotection by interleukin-6 is mediated by signal transducer and activator of transcription 3 and antioxidative signaling in ischemic stroke.

Jung Joo Eun JE   Kim Gab Seok GS   Chan Pak H PH  

Stroke 20110922 12


<h4>Background and purpose</h4>Interleukin-6 (IL-6) has been shown to have a neuroprotective effect in brain ischemic injury. However, its molecular mechanisms are still poorly understood. In this study, we investigated the neuroprotective role of the IL-6 receptor (IL-6R) by IL-6 in the reactive oxygen species defense system after transient focal cerebral ischemia (tFCI).<h4>Methods</h4>IL-6 was injected in mice before and after middle cerebral artery occlusion. Coimmunoprecipitation assays wer  ...[more]

Similar Datasets

| S-EPMC7280146 | biostudies-literature
| S-EPMC2654735 | biostudies-literature
| S-EPMC2195674 | biostudies-literature
| S-EPMC9128180 | biostudies-literature
| S-EPMC4400199 | biostudies-literature
| S-EPMC2703527 | biostudies-literature
| S-EPMC4366643 | biostudies-literature
| S-EPMC4831533 | biostudies-literature
| S-EPMC4866604 | biostudies-literature
| S-EPMC3197882 | biostudies-literature