Peripheral HMGB1-induced hyperalgesia in mice: Redox state-dependent distinct roles of RAGE and TLR4

J Pharmacol Sci. 2016 Feb;130(2):139-42. doi: 10.1016/j.jphs.2016.01.005. Epub 2016 Jan 23.

Abstract

Nuclear HMGB1 that contains 3 cysteine residues is acetylated and secreted to the extracellular space, promoting inflammation via multiple molecules such as RAGE and TLR4. We thus evaluated and characterized the redox state-dependent effects of peripheral HMGB1 on nociception. Intraplantar (i.pl.) administration of bovine thymus-derived HMGB1 (bt-HMGB1), all-thiol HMGB1 (at-HMGB1) or disulfide HMGB1 (ds-HMGB1) caused long-lasting mechanical hyperalgesia in mice. The hyperalgesia following i.pl. bt-HMGB1 or at-HMGB1 was attenuated by RAGE inhibitors, while the ds-HMGB1-induced hyperalgesia was abolished by a TLR4 antagonist. Thus, nociceptive processing by peripheral HMGB1 is considered dependent on its redox states.

Keywords: High mobility group box 1; Pain; Redox state.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • HMGB1 Protein / administration & dosage
  • HMGB1 Protein / physiology*
  • Hyperalgesia / genetics*
  • Mice
  • Nociception*
  • Oxidation-Reduction
  • Receptor for Advanced Glycation End Products / antagonists & inhibitors
  • Receptor for Advanced Glycation End Products / metabolism*
  • Toll-Like Receptor 4 / antagonists & inhibitors
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Ager protein, mouse
  • HMGB1 Protein
  • HMGB1 protein, mouse
  • Receptor for Advanced Glycation End Products
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4