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

研究成果: Article査読

2 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)14645-14654
ページ数10
ジャーナルFASEB Journal
34
11
DOI
出版ステータスPublished - 2020 11月 1
外部発表はい

ASJC Scopus subject areas

  • バイオテクノロジー
  • 生化学
  • 分子生物学
  • 遺伝学

フィンガープリント

「The effect of anesthetics on toll like receptor 9」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル