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image of Propofol Attenuates LPS-induced Inflammation by Suppressing the Activation of Histone Lactylation in hCMEC/D3 Cells

Abstract

Introduction

Neuroinflammation is recognized as one of the pathogenic mechanisms underlying sepsis-associated encephalopathy (SAE). As the most commonly used anesthetic agent in the perioperative period, propofol has been demonstrated to exhibit neuroprotective and anti-inflammatory effects. This study aimed to investigate whether propofol could mitigate lipopolysaccharide (LPS)-mediated neuroinflammation and to explore the potential mechanisms.

Methods

hCMEC/D3 cells were treated with propofol, followed by LPS exposure. Western blot, ELISA, and RT-qPCR were used to assess the expression (both protein and mRNA levels) of potential pathway participants. Intracellular Fe2+ levels were determined using an Iron Assay Kit. In addition, an blood-brain barrier (BBB) model was constructed by co-culturing hCMEC/D3 cells and human astrocytes, and BBB permeability was assessed by measuring trans-endothelial electrical resistance (TEER).

Results

LPS (50 μg/mL, 1 h) significantly increased the secretion of TNF-α and IL-1β, induced intracellular Fe2+ accumulation, and upregulated the expression of 4-HNE, H3K18la, pan-Kla, and LDHA, while decreasing the expression of ZO-1, Claudin-5, and Occludin in hCMEC/D3 cells. More importantly, propofol (25 μM, 2 h) alleviated the aforementioned effects of LPS on hCMEC/D3 cells. Furthermore, we observed significant LPS-induced TEER reduction in the BBB model, and this effect was attenuated by propofol pretreatment.

Discussion

The protective effect of propofol on hCMEC/D3 cells' ferroptosis and LDHA-lactylation induced by LPS may be an important mechanism for neuroinflammation.

Conclusion

Propofol inhibits LPS-induced lactylation, ferroptosis, and release of inflammatory cytokines in hCMEC/D3 cells by downregulating the expression of LDHA.

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2025-12-30
2026-01-26

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Propofol Attenuates LPS-induced Inflammation by Suppressing the Activation of Histone Lactylation in hCMEC/D3 Cells
Bentham Science Publishers ; https://doi.org/10.2174/0115672026423091251211090557
/content/journals/cnr/10.2174/0115672026423091251211090557
/content/journals/cnr/10.2174/0115672026423091251211090557
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  • Article Type:     Research Article
Keywords: Lipopolysaccharide ; lactylation ; Propofol ; inflammation ; hCMEC/D3 cells ; ferroptosis

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