English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

We previously reported that astrocyte-derived proinflammatory cytokine interleukin (IL)-17A could aggravate neuronal ischemic injuries and strength autophagy both in oxygen-glucose deprivation (OGD)/reoxygenation (R)-treated neurons and peri-infarct region of mice with middle cerebral artery occlusion (MCAO)/reperfusion (R)-simulated ischemic stroke. In this study, the role and molecular mechanism of IL-17A in autophagy were further explored under ischemic condition. We found that exogenous addition of rmIL-17A remarkably ( P  < 0.001) decreased cell viability, which companying with the increases of LC3 II accumulation ( P  < 0.05 or 0.01) and Beclin 1 levels ( P  < 0.05 or 0.001), and reduction of p62 levels ( P  < 0.01 or 0.001) in OGD/R-treated cortical neurons ( n  = 6). The levels of P-mTOR (Ser 2448) ( P  < 0.001) and P-S6 (Ser 240/244) ( P  < 0.01) significantly decreased without the involvement of Akt, ERK1/2 and AMPK in cortical neurons under rmIL-17A and OGD/R treatments ( n  = 6). Interestingly, the co-IP analysis exhibited that PP2B and mTOR could be reciprocally immunoprecipitated; and the addition of rmIL-17A increased their interactions, PP2B activities ( P  < 0.001), P-Src ( P  < 0.001), and P-PLCγ1 ( P  < 0.01) levels in OGD/R-treated neurons ( n  = 6 or 5). The PP2B inhibitor Cyclosporin A blocked the induction of excessive autophagy ( P  < 0.05 or <0.001) and increased cell viability ( P  < 0.001) after OGD/R and rmIL-17A treatments ( n  = 6). In addition, the ICV injection of IL-17A neutralizing mAb could attenuate autophagy levels ( P  < 0.01 or 0.001,  n  = 6) and improve neurological functions ( P  < 0.01 or 0.001,  n  = 10) of mice after 1 h MCAO/R 24 h or 7 d. These results suggested that IL-17A-mediated excessive autophagy aggravates neuronal ischemic injuries via Src-PP2B-mTOR pathway, and IL-17A neutralization may provide a potential therapeutic effect for ischemic stroke.

IL-17A-Mediated Excessive Autophagy Aggravated Neuronal Ischemic Injuries via Src-PP2B-mTOR Pathway