LAUSR

OBJECTIVE Evidences had demonstrated that propofol attenuated neuro-inflammation following brain ischemia. Moreover, LncRNA-MEG3 was identified as an independent prognostic marker for ischemic stroke patients, and was found to be correlated with cerebral ischemia in animal models. Therefore, the current study explored the role of propofol on lipopolysaccharide (LPS)-mediated inflammation in cultured astrocytes, along with the molecular mechanism involved in LncRNA-MEG3/NF-κB axis. METHODS The primary cultured astrocytes isolated from rats were used to establish an inflammatory model, which were treated with LPS. Propofol was administrated to the primary cultured astrocytes during LPS treatment. The effect of propofol on pro-inflammatory cytokines and the LncRNA-MEG3/NF-κB pathway were detected by ELISA, qRT-PCR and Western Blot assay, respectively. Then, dual-luciferase assay, chromatin immunoprecipitation and RNA immunoprecipitation were used to determine the interaction between LncRNA-MEG3 and NF-κB. RESULTS Our study found that propofol significantly reduced LncRNA-MEG3 expression, which was elevated in LPS-stimulated astrocytes. Moreover, both propofol and LncRNA-MEG3 knockdown remarkably alleviated LPS-induced cytotoxicity by suppressing expressions and release of pro-inflammatory cytokines. Loss of LncRNA-MEG3 notably suppressed the NF-κB activity and its phosphorylated activation. Additionally, it was also observed that LncRNA-MEG3 could bind nuclear p65/p50, and promote the binding of NF-κB to IL-6 and TNF-α promoters in the nucleus, subsequently stimulating the production of inflammatory cytokines in LPS-treated astrocytes. Furthermore, a specific inhibitor of NF-κB, PDTC rescued astrocytes from LPS exposure without affecting LncRNA-MEG3 expression. CONCLUSION These findings demonstrated that LncRNA-MEG3 acted as a positive regulator of NF-κB, mediated the neuroprotection of propofol in LPS-triggered astrocytes injury.