title: HMGB1-DNA complex-induced autophagy limits AIM2 inflammasome activation through RAGE.
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.
authors: 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.
authors: Liying
authors: L
authors: Liu
authors: Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors: Minghua
authors: M
authors: Yang
authors: Department of Surgery, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15219, USA.
authors: Rui
authors: R
authors: Kang
authors: Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.
authors: Yunpeng
authors: Y
authors: Dai
authors: Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Department of Surgery, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15219, USA.
authors: Yan
authors: Y
authors: Yu
authors: Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.
authors: Fei
authors: F
authors: Gao
authors: Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.
authors: Hongmei
authors: H
authors: Wang
authors: Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.
authors: Xiaojun
authors: X
authors: Sun
authors: Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.
authors: Xiuli
authors: X
authors: Li
authors: The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030, USA.
authors: Jianhua
authors: J
authors: Li
authors: The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030, USA.
authors: Haichao
authors: H
authors: Wang
authors: Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. Electronic address: lizhicao@gmail.com.
authors: Lizhi
authors: L
authors: Cao
authors: Department of Surgery, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15219, USA. Electronic address: tangd2@upmc.edu.
authors: Daolin
authors: D
authors: Tang
mesh_terms: D001343:Autophagy / Q000276:immunology*; D004247:DNA / Q000276:immunology*; D004268:DNA-Binding Proteins; D018922:HL-60 Cells; D024243:HMGB1 Protein / Q000276:immunology*; D006801:Humans; D058847:Inflammasomes / Q000276:immunology*; D018836:Inflammation Mediators / Q000276:immunology*; D009687:Nuclear Proteins / Q000276:immunology*; D000067759:Receptor for Advanced Glycation End Products / Q000276:immunology*
chemical_list: C000593871:AGER protein, human; C410167:AIM2 protein, human; D004268:DNA-Binding Proteins; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D058847:Inflammasomes; D018836:Inflammation Mediators; D009687:Nuclear Proteins; D000067759:Receptor for Advanced Glycation End Products; D004247:DNA
keywords: AIM2; Autophagy; DNA; HMGB1; Inflammasome; RAGE