HMGB1-DNA complex-induced autophagy limits AIM2 inflammasome activation through RAGE.
Article Details
- CitationCopy to clipboard
Liu L, Yang M, Kang R, Dai Y, Yu Y, Gao F, Wang H, Sun X, Li X, Li J, Wang H, Cao L, Tang D
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. Epub 2014 Jun 24.
- PubMed ID
- 24971542 [ View in PubMed]
- 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 1beta (IL-1beta). Subsequently, HMGB1-DNA complex stimulated an ATG5-dependent cellular degradation process, autophagy, which was paralleled by a cessation of AIM2 inflammasome activation and IL-1beta 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.