Giuliani Anna Lisa, Sarti Alba C, Falzoni Simonetta, Di Virgilio Francesco
Department of Morphology, Surgery and Experimental Medicine, University of Ferrara Ferrara, Italy.
Front Pharmacol. 2017 Mar 16;8:123. doi: 10.3389/fphar.2017.00123. eCollection 2017.
Interleukin-1β (IL-1β) 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-1β synthesis and release is particularly relevant for the design of novel anti-inflammatory drugs. One of the molecules mainly involved in IL-1β 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-1β 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.
白细胞介素-1β（IL-1β）在刺激先天性免疫系统和炎症以及多种慢性炎症性疾病中发挥核心作用。这些疾病包括罕见的遗传性疾病，如自身炎症综合征，以及常见的病症，如II型糖尿病、痛风和动脉粥样硬化。更好地理解IL-1β的合成和释放对于新型抗炎药物的设计尤为重要。主要参与IL-1β成熟的分子之一是P2X7受体（P2X7R），它是一种ATP门控离子通道，主要通过募集NLRP3炎性小体-半胱天冬酶-1复合物发挥作用。在这篇综述中，我们将总结支持P2X7R在IL-1β产生中关键作用的证据，特别强调释放机制，这一过程仍然存在争议。已经提出了四种不同的模型：（i）通过分泌性溶酶体的胞吐作用，（ii）从质膜脱落的微泡，（iii）外泌体的释放，以及（iv）在细胞焦亡期间通过渗漏的质膜被动流出。所有这些模型都涉及P2X7R。
