Journal
FRONTIERS IN PHARMACOLOGY
Volume 8, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2017.00123
Keywords
interleukin-1 b; P2X7 receptor; NLRP3 inflammasome; caspase-1; inflammation
Categories
Funding
- Italian Association for Cancer Research [IG 13025, IG 18581]
- Telethon of Italy [GGP06070]
- ERA-NET Neuron Joint Transnational Project Nanostroke
- Ministry of Health of Italy [RF-2011-02348435]
- Italian Ministry of Education, University and Research [RBAP11FXBC_001]
- University of Ferrara
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Interleukin-1 b (IL-1 beta) plays a central role in stimulation of innate immune system and inflammation and in several chronic inflammatory diseases. These include rare hereditary conditions, e.g., auto-inflammatory syndromes, as well as common pathologies, such as type II diabetes, gout and atherosclerosis. A better understanding of IL-1 b synthesis and release is particularly relevant for the design of novel anti-inflammatory drugs. One of the molecules mainly involved in IL-1 beta maturation is the P2X7 receptor (P2X7R), an ATP-gated ion channel that chiefly acts through the recruitment of the NLRP3 inflammasome-caspase-1 complex. In this review, we will summarize evidence supporting the key role of the P2X7R in IL-1 beta production, with special emphasis on the mechanism of release, a process that is still a matter of controversy. Four different models have been proposed: (i) exocytosis via secretory lysosomes, (ii) microvesicles shedding from plasma membrane, (iii) release of exosomes, and (iv) passive efflux across a leaky plasma membrane during pyroptotic cell death. All these models involve the P2X7R.
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