HMGB1-DNA complex-induced autophagy limits AIM2 inflammasome activation through RAGE

Liying Liu, Minghua Yang, Rui Kang, Yunpeng Dai, Yan Yu, Fei Gao, Hongmei Wang, Xiaojun Sun, Xiuli Li, Jianhua Li, Haichao Wang, Lizhi Cao, Daolin Tang

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

High mobility group box 1 (HMGB1) is a prototype damage-associated molecular pattern (DAMP) that can induce inflammatory and immune responses alone as well as in combination with other molecules such as DNA. However, the intricate molecular mechanisms underlying HMGB1-DNA complex-mediated innate immune response remains largely elusive. In this study, we demonstrated that HMGB1-DNA complex initially induced absent in melanoma 2 (AIM2)-dependent inflammasome activation, and promoted rapid release of inflammasome-dependent early proinflammatory cytokines such as interleukin 1β (IL-1β). Subsequently, HMGB1-DNA complex stimulated an ATG5-dependent cellular degradation process, autophagy, which was paralleled by a cessation of AIM2 inflammasome activation and IL-1β release. These HMGB1-DNA complex-induced inflammasome activation and autophagy were both dependent on the receptor for advanced glycation endproducts (RAGE) that recognizes a wide array of ligands (including HMGB1 and DNA). Thus, autophagy may function as a negative counter-regulatory mechanism for HMGB1-DNA complex-induced inflammasome activation, and provide a checkpoint to limit the development of inflammation.

Original languageEnglish (US)
Pages (from-to)851-856
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume450
Issue number1
DOIs
StatePublished - Jul 18 2014
Externally publishedYes

Keywords

  • AIM2
  • Autophagy
  • DNA
  • HMGB1
  • Inflammasome
  • RAGE

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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