The effect of anesthetics on toll like receptor 9

Sophia Koutsogiannaki, Weiming Bu, Lifei Hou, Miho Shibamura-Fujiogi, Hanako Ishida, Umeharu Ohto, Roderic G. Eckenhoff, Koichi Yuki

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)14645-14654
Number of pages10
JournalFASEB Journal
Volume34
Issue number11
DOIs
Publication statusPublished - 2020 Nov 1
Externally publishedYes

Keywords

  • electrostatic potential
  • nucleic acid
  • toll-like receptor
  • volatile anesthetics

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint

Dive into the research topics of 'The effect of anesthetics on toll like receptor 9'. Together they form a unique fingerprint.

Cite this