Microglial and Neuronal Cell Pyroptosis Induced by Oxygen-Glucose Deprivation/Reoxygenation Aggravates Cell Injury via Activation of the Caspase-1/GSDMD Signaling Pathway

by Selleckchem | Jul 25 2023

Pyroptosis is a new type of programmed cell death, which induces a strong pro-inflammatory reaction. However, the mechanism of pyroptosis after brain ischemia/reperfusion (I/R) and the interaction between different neural cell types are still unclear. This study comprehensively explored the mechanisms and interactions of microglial and neuronal pyroptosisin the simulated I/R environment in vitro. The BV2 (as microglial) and HT22(as neuronal) cells were treated by oxygen-glucose deprivation/reoxygenation (OGD/R). Both BV2 and HT22 cells underwent pyroptosis after OGD/R, and the pyroptosis occurred at earlier time point in HT22than that of BV2. Caspase-11 and Gasdermin E expression in BV2 and HT22 cells did not change significantly after OGD/R. Inhibition of caspase-1 or GSDMD activity, or down-regulation of GSDMD expression, alleviated pyroptosis in both BV2 and HT22 cells after OGD/R. Transwell studies further showed that OGD/R-treated HT22 or BV2 cells aggravated pyroptosis of adjacent non-OGD/R-treated cells, which could be relieved by inhibition of caspase-1 or GSDMD. These results suggested that OGD/R induces pyroptosis of microglia and neuronal cells and aggravates cell injury via activation of caspase-1/GSDMD signaling pathway. Our findings indicated that caspase-1 and GSDMD may be therapeutic targets after cerebral I/R.

Comments:

The study you mentioned aimed to investigate the mechanisms and interactions of pyroptosis in microglial and neuronal cells under simulated ischemia/reperfusion (I/R) conditions. Pyroptosis is a form of programmed cell death characterized by the release of pro-inflammatory factors. The researchers used BV2 cells (microglial cells) and HT22 cells (neuronal cells) and subjected them to oxygen-glucose deprivation/reoxygenation (OGD/R), which mimics the conditions experienced during I/R.

The results of the study showed that both BV2 and HT22 cells underwent pyroptosis after OGD/R, indicating that this form of cell death occurs in both microglial and neuronal cells under ischemic conditions. However, the onset of pyroptosis was observed earlier in HT22 cells compared to BV2 cells.

The expression of caspase-11 and Gasdermin E (GSDME) in BV2 and HT22 cells did not show significant changes after OGD/R. Caspase-1 and GSDMD are key components of the pyroptosis signaling pathway. Inhibition of caspase-1 or GSDMD activity, as well as down-regulation of GSDMD expression, alleviated pyroptosis in both BV2 and HT22 cells following OGD/R. These findings suggest that caspase-1 and GSDMD play crucial roles in the induction of pyroptosis in microglial and neuronal cells after ischemic insult.

Furthermore, the researchers conducted transwell studies, where OGD/R-treated HT22 or BV2 cells were co-cultured with non-OGD/R-treated cells. It was observed that the OGD/R-treated cells aggravated pyroptosis in the adjacent non-OGD/R-treated cells, indicating a detrimental effect of the ischemic environment on neighboring cells. However, this aggravation of pyroptosis could be relieved by inhibiting caspase-1 or GSDMD activity.

In summary, the study highlights that OGD/R induces pyroptosis in microglial and neuronal cells and exacerbates cell injury through the activation of the caspase-1/GSDMD signaling pathway. The findings suggest that targeting caspase-1 and GSDMD may have therapeutic potential in the context of cerebral ischemia/reperfusion injury.