Lysophosphatidylcholine induces apoptosis and inflammatory damage in brain microvascular endothelial cells via GPR4-mediated NLRP3 inflammasome activation.

Lysophosphatidylcholine (LPC), as the main active component of oxidized low-density lipoproteins (ox-LDLs), has significant effects in cerebrovascular disease. However, the complex mechanism by which LPC functions in brain microvascular endothelial cells (BMECs) is not clearly understood. In this study, BMECs were transfected with G protein-coupled receptor 4 (GPR4) siRNA or an NLRP3-overexpression plasmid, and GPR4 expression was identified by RT-qPCR and western blotting; IL-1β, IL-18, and IL-33 levels were evaluated by ELISA. Apoptosis was monitored by flow cytometry and Hoechst staining, while Caspase 3, ASC, NLRP3, and GPR4 protein expression were examined by western blotting. Our results showed that LPC significantly increased the levels of inflammatory cytokines (IL-1β, IL-18, and IL-33) and markedly induced apoptosis and NLRP3 inflammasome activation in BMECs. Moreover, LPC notably upregulated GPR4 in BMECs, and knockdown of GPR4 significantly attenuated the effects of LPC in BMECs. Above all, we also proved that LPC induced apoptosis and inflammatory injury in BMECs by causing GPR4 to activate NLRP3 inflammasomes. Therefore, GPR4-mediated activation of NLRP3 inflammasomes might be the underlying mechanism by which LPC promotes the progression of cerebrovascular disease. In summary we found that LPC is an important pathogenic factor in cerebrovascular disease, and can induce GPR4 to active NLRP3 inflammasomes.