The effect of anesthetics on toll like receptor 9.
electrostatic potential
nucleic acid
toll-like receptor
volatile anesthetics
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
02
04
2020
revised:
17
08
2020
accepted:
20
08
2020
pubmed:
10
9
2020
medline:
1
5
2021
entrez:
9
9
2020
Statut:
ppublish
Résumé
Toll like receptors (TLRs) are critical receptors to respond to danger signals, and their functions are relevant in the perioperative period. We previously reported that volatile anesthetics directly bound to TLR2 and TLR4 and attenuated their functions. Given that TLR9 can respond to mitochondrial DNA, a danger signal that is released upon tissue injury, we examined the role of anesthetics on TLR9 function. Our reporter assay showed that volatile anesthetics isoflurane and sevoflurane increased the activation of TLR9, while propofol attenuated it. TLR9 activation occurs via its dimerization. The dimerization is facilitated by unmethylated cytosine-phosphate-guanine (CpG) DNA as well as DNA containing cytosine at the second position from 5'-end (5'-xCx DNA). Our structural analysis using photoactivable anesthetics and rigid docking simulation showed that isoflurane and sevoflurane bound to both TLR9 dimer interface and 5'-xCx DNA binding site. Propofol bound to the TLR9 antagonist binding site. This is the first illustration that anesthetics can affect the binding of nucleic acids to their receptor. This study sets the foundation for the effect of anesthetics on TLR9 and will pave the way for future studies to determine the significance of such interactions in the clinical setting.
Identifiants
pubmed: 32901993
doi: 10.1096/fj.202000791RR
pmc: PMC7814252
mid: NIHMS1660252
doi:
Substances chimiques
Anesthetics, Inhalation
0
Toll-Like Receptor 9
0
Sevoflurane
38LVP0K73A
Isoflurane
CYS9AKD70P
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
14645-14654Subventions
Organisme : NICHD NIH HHS
ID : R21 HD099194
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM127600
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM118277
Pays : United States
Informations de copyright
© 2020 Federation of American Societies for Experimental Biology.
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