Background
The T cell Ig domain and mucin domain (TIM)-1 protein expressed on the surface of Th2 cells regulates the immune response by modulating cytokine production. The present study aimed to investigate the role and possible mechanism of TIM-1 in cerebral ischemia-reperfusion injury.
Conclusion
Take together, these results indicated that TIM-1 blockade ameliorated cerebral ischemia-reperfusion injury. Thus, TIM-1 disruption may serve as a novel target for therapy following MCAO.
Methods
Western blot was used to detect TIM-1 and apoptosis-related protein expression, whereas TIM-1 mRNA was examined using quantitative real-time reverse transcription PCR. Flow cytometry and a TdT-mediated biotin-16-dUTP nick-end labeling (TUNEL) assay were used to detect the percentage of apoptotic cells and a pathological examination was performed. The migration of neutrophils and macrophages was analyzed by immunohistochemistry.
Results
Our results suggest that TIM-1 expression was transiently increased 24 h or 48 h following middle cerebral artery occlusion (MCAO)/reperfusion. The infarct size was markedly increased in MCAO, whereas treatment with a TIM-1-blocking mAb could reduce the infarct size. TIM-1 blocking mAb effectively reduced the number of neutrophils, macrophage functionality, cytokine (i.e., IL-6, IL-1β, and TNF-α) and chemokine (i.e., CXCL-1 and CXCL-2) production in the brain tissue. The effect of in vitro T cell damage on neurons was significantly reduced following treatment with a TIM-1 blocking mAb or the knockdown of TIM-1 in co-cultured T cells and neurons.