Publication Date
2014
Journal Title
Biochem Biophys Res Commun
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 10 (IL-1 beta). Subsequently, HMGB1 - DNA complex stimulated an ATG5-dependent cellular degradation process, autophagy, which was paralleled by a cessation of AIM2 inflammasome activation and IL-1 beta 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. (C) 2014 Elsevier Inc. All rights reserved.
Volume Number
450
Issue Number
1
Pages
851-856
Document Type
Article
Status
Faculty, Northwell Researcher
Facility
School of Medicine; Northwell Health
Primary Department
Emergency Medicine
PMID
DOI
10.1016/j.bbrc.2014.06.074