title: Peripheral HMGB1-induced hyperalgesia in mice: Redox state-dependent distinct roles of RAGE and TLR4.
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.
authors.affiliation: Laboratory of Pharmacology and Pathophysiology, Faculty of Pharmacy, Kindai University (formerly Kinki University), Higashi-Osaka 577-8502, Japan.
authors.forename: Daichi
authors.initials: D
authors.lastname: Yamasoba
authors.affiliation: Laboratory of Pharmacology and Pathophysiology, Faculty of Pharmacy, Kindai University (formerly Kinki University), Higashi-Osaka 577-8502, Japan.
authors.forename: Maho
authors.initials: M
authors.lastname: Tsubota
authors.affiliation: Laboratory of Pharmacology and Pathophysiology, Faculty of Pharmacy, Kindai University (formerly Kinki University), Higashi-Osaka 577-8502, Japan.
authors.forename: Risa
authors.initials: R
authors.lastname: Domoto
authors.affiliation: Laboratory of Pharmacology and Pathophysiology, Faculty of Pharmacy, Kindai University (formerly Kinki University), Higashi-Osaka 577-8502, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Sekiguchi
authors.affiliation: Laboratory of Pharmacology and Pathophysiology, Faculty of Pharmacy, Kindai University (formerly Kinki University), Higashi-Osaka 577-8502, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishikawa
authors.affiliation: Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
authors.forename: Keyue
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nishibori
authors.affiliation: Department of Emergency and Critical Care Medicine, Fukuoka University Hospital, Fukuoka 814-0180, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Ishikura
authors.affiliation: Laboratory of Pathological and Biomolecule Analyses, Faculty of Pharmacy, Kindai University (formerly Kinki University), Higashi-Osaka 577-8502, Japan.
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Laboratory of Pathological and Biomolecule Analyses, Faculty of Pharmacy, Kindai University (formerly Kinki University), Higashi-Osaka 577-8502, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Taga
authors.affiliation: Laboratory of Pharmacology and Pathophysiology, Faculty of Pharmacy, Kindai University (formerly Kinki University), Higashi-Osaka 577-8502, Japan. Electronic address: kawabata@phar.kindai.ac.jp.
authors.forename: Atsufumi
authors.initials: A
authors.lastname: Kawabata
mesh_terms: D000818:Animals; D002417:Cattle; D024243:HMGB1 Protein / Q000008:administration & dosage / Q000502:physiology*; D006930:Hyperalgesia / Q000235:genetics*; D051379:Mice; D059225:Nociception; D010084:Oxidation-Reduction; D000067759:Receptor for Advanced Glycation End Products / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C000593873:Ager protein, mouse; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D000067759:Receptor for Advanced Glycation End Products; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4
keywords: High mobility group box 1; Pain; Redox state