作者
James Harris, Michelle Hartman, Caitrionna Roche, Shijuan G Zeng, Amy O'Shea, Fiona A Sharp, Eimear M Lambe, Emma M Creagh, Douglas T Golenbock, Jurg Tschopp, Hardy Kornfeld, Katherine A Fitzgerald, Ed C Lavelle
发表日期
2011/3/18
期刊
Journal of Biological Chemistry
卷号
286
期号
11
页码范围
9587
出版商
American Society for Biochemistry and Molecular Biology
简介
Autophagy is a key regulator of cellular homeostasis that can be activated by pathogen-associated molecules and recently has been shown to influence IL-1β secretion by macrophages. However, the mechanisms behind this are unclear. Here, we describe a novel role for autophagy in regulating the production of IL-1β in antigen-presenting cells. After treatment of macrophages with Toll-like receptor ligands, pro-IL-1β was specifically sequestered into autophagosomes, whereas further activation of autophagy with rapamycin induced the degradation of pro-IL-1β and blocked secretion of the mature cytokine. Inhibition of autophagy promoted the processing and secretion of IL-1β by antigen-presenting cells in an NLRP3- and TRIF-dependent manner. This effect was reduced by inhibition of reactive oxygen species but was independent of NOX2. Induction of autophagy in mice in vivo with rapamycin reduced serum …
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J Harris, M Hartman, C Roche, SG Zeng, A O'Shea… - Journal of Biological Chemistry, 2011