HMGB1-DNA complex-induced autophagy limits AIM2 inflammasome activation through RAGE.
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| 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.
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| Authors | 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 |
| Journal | Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 450 Issue 1 Pg. 851-6 (Jul 18 2014) ISSN: 1090-2104 [Electronic] United States |
| PMID | 24971542 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2014 Elsevier Inc. All rights reserved. |
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