Referenced in: none

Automatically associated channels: TRP , TRPC , TRPC6

Title: IL-17A contributes to brain ischemia reperfusion injury through calpain-TRPC6 pathway in mice.

Authors: Jiancheng Zhang, Xiaobo Mao, Ting Zhou, Xiang Cheng, Yun Lin

Journal, date & volume: Neuroscience, 2014 Aug 22 , 274, 419-28

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24928352

Abstract
Interleukin (IL)-17A plays an important role in the cerebral ischemia/reperfusion (I/R) injury. However, the mechanisms are still largely unknown. Calpain-transient receptor potential canonical (subtype) 6 (TRPC6) signaling pathway has been recently found to be implicated in brain I/R injury. However, their relationships with IL-17A remain unknown. This study aims to test whether this important signaling has correlation with IL-17A and how they led to the neuronal damage in I/R injury. In the present study, mice were subjected to middle cerebral artery occlusion (60 min) followed by reperfusion for different times. Infarct volumes and neurological deficits were examined. Real-time PCR (RT-PCR) and Western blotting were conducted to detect IL-17A expression in the penumbral brain tissue. Activation of calpain and expression of TRPC6 were also studied. We found that cerebral I/R significantly increased the levels of IL-17A at 1, 3 and 6 days after reperfusion in the penumbral area. IL-17A knockout or anti-IL-17A monoclonal antibody (mAb) significantly reduced whereas recombinant mouse-IL-17A (rIL-17A) increased the activation of calpain at 3 days after reperfusion. The calpain specific inhibitor calpeptin significantly increased TRPC6 expression. Brain injury and neurological deficits were largely abrogated by IL-17A knockout, anti-IL-17A mAb or calpeptin. Recombinant IL-17A treatment markedly increased I/R injury. In conclusion, IL-17A may promote brain I/R injury through the increase of calpain-mediated TRPC6 proteolysis. These results further outline a novel neuroprotective strategy with increased effectiveness for the inhibition of excess brain IL-17A in cerebral I/R injury.