ArticleJournal of translational medicine2024
Propofol improves survival in a murine model of sepsis via inhibiting Rab5a-mediated intracellular trafficking of TLR4.
Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 3 citations in OpenAlex.
- Skin delivery and anti-inflammatory effects of the anesthetic propofol against psoriasiform lesions through KEAP1/Nrf2/HO-1 pathway activation.Cellular and molecular life sciences : CMLS · 2025Article
- Impact of General Anesthetics on Postoperative Infections-A Narrative Review.Life (Basel, Switzerland) · 2025Review
- Evaluation of the protective role of resveratrol on LPS-induced septic intestinal barrier function via TLR4/MyD88/NF-κB signaling pathways.Scientific reports · 2025Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPropofol is a widely used anesthetic and sedative, which has been reported to exert an anti-inflammatory effect. TLR4 plays a critical role in coordinating the immuno-inflammatory response during sepsis. Whether propofol can act as an immunomodulator through regulating TLR4 is still unclear. Given its potential as a sepsis therapy, we investigated the mechanisms underlying the immunomodulatory activity of propofol.
methodsThe effects of propofol on TLR4 and Rab5a (a master regulator involved in intracellular trafficking of immune factors) were investigated in macrophage (from Rab5a
resultsWe showed that propofol reduced membrane TLR4 expression on macrophages in vitro and in vivo. Rab5a participated in TLR4 intracellular trafficking and both Rab5a expression and the interaction between Rab5a and TLR4 were inhibited by propofol. We also showed Rab5a upregulation in peripheral blood monocytes of septic patients, accompanied by increased TLR4 expression on the cell surface. Propofol downregulated the expression of Rab5a and TLR4 in these cells.
conclusionsWe demonstrated that Rab5a regulates intracellular trafficking of TLR4 and that propofol reduces membrane TLR4 expression on macrophages by targeting Rab5a. Our study not only reveals a novel mechanism for the immunomodulatory effect of propofol but also indicates that Rab5a may be a potential therapeutic target against sepsis.
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