2. Academic Validation
  3. HMGB1-DNA complex-induced autophagy limits AIM2 inflammasome activation through RAGE

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

  • Biochem Biophys Res Commun. 2014 Jul 18;450(1):851-6. doi: 10.1016/j.bbrc.2014.06.074.
Liying Liu 1,  Minghua Yang 2,  Rui Kang 3,  Yunpeng Dai 4,  Yan Yu 5,  Fei Gao 4,  Hongmei Wang 4,  Xiaojun Sun 4,  Xiuli Li 4,  Jianhua Li 6,  Haichao Wang 6,  Lizhi Cao 7,  Daolin Tang 8
Affiliations

Affiliations

  • 1 Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China; Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
  • 2 Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
  • 3 Department of Surgery, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15219, USA.
  • 4 Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.
  • 5 Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Department of Surgery, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15219, USA.
  • 6 The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030, USA.
  • 7 Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. Electronic address: lizhicao@gmail.com.
  • 8 Department of Surgery, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15219, USA. Electronic address: tangd2@upmc.edu.
PMID: 24971542 DOI: 10.1016/j.bbrc.2014.06.074
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.

Keywords

AIM2; Autophagy; DNA; HMGB1; Inflammasome; RAGE.

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