期刊
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
卷 83, 期 -, 页码 12-21出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcdb.2018.03.011
关键词
IL-1 beta; Vesicular secretion; Secretory lysosomes; Autophagy; Gasdermin D
资金
- Italian Ministry of Health 'Cinque per mille' and Ricerca Corrente
- Telethon, Italy [GGP14144, GGP15059]
- Fondazione Cariplo [2015-0591]
- Associazione Italiana per la Ricerca sul Cancro [IG 2016-15434, IG 2016-18824]
Interleukin 1 beta (IL-1 beta) is a major mediator of inflammation, with a causative role in many diseases. Unlike most other cytokines, however, it lacks a secretory signal sequence, raising intriguing mechanistic, functional and evolutionary questions. Despite decades of strenuous efforts in many laboratories, how IL-1 beta is secreted is still a matter of intense debate. Here, we summarize the different mechanisms and pathways that have been proposed for IL-1 beta secretion. At least two of them, namely the endolysosomal vesicle-based and gasdermin D-dependent pathways (types III and I in the recent Rabouille's classification of unconventional protein secretion), can be triggered in monocytes, the main source of IL-1 beta in humans, according to the type and strength of the pro-inflammatory stimuli. As during the escalation of human conflicts, monocytes deploy secretory mechanisms of increasing efficiency and dangerousness, shifting from the specific and controlled type III pathway to the much faster release of type I. Thus, the different mechanisms are activated depending on the severity of the conditions, from the self-limiting type III pathways in response of low pathogen load or small trauma, to the uncontrolled responses that underlie autoinflammatory disorders and sepsis. (C) 2018 Elsevier Ltd. All rights reserved.
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