Chloroquine inhibits HMGB1 inflammatory signaling and protects mice from lethal sepsis

Minghua Yang, Lizhi Cao, Min Xie, Yan Yu, Rui Kang, Liangchun Yang, Mingyi Zhao, Daolin Tang

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Sepsis is caused by an overwhelming immune response to bacterial infection. The discovery of high mobility group box 1 (HMGB1) as a late mediator of lethal sepsis has prompted investigation into the development of new therapeutics which specifically target this protein. Here, we show that chloroquine, an anti-malarial drug, prevents lethality in mice with established endotoxemia or sepsis. This effect is still observed even if administration of chloroquine is delayed. The protective effects of chloroquine were mediated through inhibition of HMGB1 release in macrophages, monocytes, and endothelial cells, thereby preventing its cytokine-like activities. As an inhibitor of autophagy, chloroquine specifically inhibited HMGB1-induced Ik-B degradation and NF-kB activation. These findings define a novel mechanism for the anti-inflammatory effects of chloroquine and also suggest a new potential clinical use for this drug in the setting of sepsis. Crown

Original languageEnglish (US)
Pages (from-to)410-418
Number of pages9
JournalBiochemical Pharmacology
Volume86
Issue number3
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

Fingerprint

Chloroquine
Sepsis
Endotoxemia
NF-kappa B
Macrophages
Endothelial cells
Autophagy
Antimalarials
Crowns
Bacterial Infections
Pharmaceutical Preparations
Monocytes
Anti-Inflammatory Agents
Endothelial Cells
Chemical activation
Cytokines
Degradation
Proteins

Keywords

  • Autophagy
  • Beclin 1
  • Chloroquine
  • HMGB1
  • NF-kB
  • Sepsis

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Cite this

Chloroquine inhibits HMGB1 inflammatory signaling and protects mice from lethal sepsis. / Yang, Minghua; Cao, Lizhi; Xie, Min; Yu, Yan; Kang, Rui; Yang, Liangchun; Zhao, Mingyi; Tang, Daolin.

In: Biochemical Pharmacology, Vol. 86, No. 3, 01.01.2013, p. 410-418.

Research output: Contribution to journalArticle

Yang, Minghua ; Cao, Lizhi ; Xie, Min ; Yu, Yan ; Kang, Rui ; Yang, Liangchun ; Zhao, Mingyi ; Tang, Daolin. / Chloroquine inhibits HMGB1 inflammatory signaling and protects mice from lethal sepsis. In: Biochemical Pharmacology. 2013 ; Vol. 86, No. 3. pp. 410-418.
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