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

24971542

DOI

10.1016/j.bbrc.2014.06.074


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