Dexmedetomidine directly binds to and inhibits Toll-like receptor 4
Issued Date
2024-11-15
Resource Type
ISSN
15675769
eISSN
18781705
Scopus ID
2-s2.0-85201716578
Pubmed ID
39163686
Journal Title
International Immunopharmacology
Volume
141
Rights Holder(s)
SCOPUS
Bibliographic Citation
International Immunopharmacology Vol.141 (2024)
Suggested Citation
Koutsogiannaki S., Limratana P., Bu W., Maisat W., McKinstry-Wu A., Han X., Ohto U., Eckenhoff R.G., Soriano S.G., Yuki K. Dexmedetomidine directly binds to and inhibits Toll-like receptor 4. International Immunopharmacology Vol.141 (2024). doi:10.1016/j.intimp.2024.112975 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/100675
Title
Dexmedetomidine directly binds to and inhibits Toll-like receptor 4
Corresponding Author(s)
Other Contributor(s)
Abstract
Background: While a number of anesthetics has been shown potentially associated with neurotoxicity in the developing brain, dexmedetomidine, a drug that was rather recently introduced into the perioperative setting, is considered beneficial from neurological wellbeing. However, the underlying mechanism of how dexmedetomidine affects brain health remains to be determined. Based on our recent study, we hypothesized that dexmedetomidine would directly bind to and inhibit Toll-like receptor 4 (TLR4), a critical receptor largely expressed in microglia and responsible for neurological insult. Methods: We used TLR4 reporter assays to test if dexmedetomidine attenuates TLR4 activation. Furthermore, a direct binding of dexmedetomidine on TLR4 was tested using photoactivatable medetomidine. Lastly, the effect of dexmedetomidine on ketamine (anesthetic)-induced neurotoxicity was tested in rat pups (P7). Results: We showed that dexmedetomidine attenuated TLR4 activation using reporter assay (IC50 = 5.8 µg/mL). Photoactivatable dexmedetomidine delineated its direct binding sites on TLR4. We also showed that dexmedetomidine attenuated microglia activation both in vitro and in vivo. Discussion: We proposed a novel mechanism of dexmedetomidine-mediated neuroprotection.