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The effect of anesthetics on toll like receptor 9

Sophia Koutsogiannaki1,2,3, Weiming Bu4, Lifei Hou1,2,3

  • 1Department of Anesthesiology, Critical Care and Pain Medicine, Cardiac Anesthesia Division, Boston Children's Hospital, Boston, MA, USA.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|September 9, 2020
PubMed

Insights

Anesthetics affect Toll-like receptor 9 (TLR9) function. Volatile anesthetics like isoflurane and sevoflurane activate TLR9, while propofol inhibits it, impacting immune responses during surgery.

Area of Science:

  • Immunology
  • Anesthesiology
  • Molecular Biology

Background:

  • Toll-like receptors (TLRs) are crucial for detecting danger signals, particularly in the perioperative setting.
  • Previous research indicated volatile anesthetics modulate TLR2 and TLR4 functions.
  • TLR9 recognizes mitochondrial DNA, a danger signal released during tissue injury.

Purpose of the Study:

  • To investigate the impact of common anesthetics on Toll-like receptor 9 (TLR9) activation.
  • To elucidate the molecular mechanisms by which anesthetics interact with TLR9.

Main Methods:

  • Reporter assays were used to measure TLR9 activation by anesthetics.
  • Structural analysis involved photoactivable anesthetics and rigid docking simulations.
  • Investigated anesthetic binding sites on TLR9 and its interaction with DNA ligands.

Main Results:

  • Isoflurane and sevoflurane enhanced TLR9 activation, whereas propofol attenuated it.
  • Structural analysis revealed isoflurane and sevoflurane bind to the TLR9 dimer interface and 5'-xCx DNA site.
  • Propofol was found to bind to the TLR9 antagonist binding site.

Conclusions:

  • This study demonstrates for the first time that anesthetics can interfere with nucleic acid binding to TLR9.
  • Anesthetics differentially modulate TLR9 activity, with implications for perioperative immune responses.
  • These findings establish a foundation for understanding anesthetic-TLR9 interactions in clinical settings.
Keywords:
electrostatic potentialnucleic acidtoll-like receptorvolatile anesthetics

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