Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, University of Ferrara, Ferrara, Italy.
Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, University of Ferrara, Ferrara, Italy.
Biochem Pharmacol. 2018 May;151:234-244. doi: 10.1016/j.bcp.2017.12.021. Epub 2017 Dec 27.
Damage associated molecular patterns (DAMPs) are intracellular molecules released from infected or injured cells to activate inflammatory and reparatory responses. One of the most ancient and conserved DAMPs is extracellular ATP that exerts its phlogistic activity mainly through activation of the P2X7 receptor (P2X7R). The P2X7R is an ATP gated ion channel, expressed by most immune cells, including the monocyte-derived cell lineages, T and B lymphocytes and their precursors. Here we give an overview of recent and established literature on the role of P2X7R in septic and sterile inflammation. P2X7R ability in restraining intracellular bacteria and parasite infection by modulation of the immune response are described, with particular focus on Mycobacteria and Plasmodium. Emerging literature on the role of P2X7 in viral infections such as HIV-1 is also briefly covered. Finally, we describe the numerous intracellular pathways related to inflammation and activated by the P2X7R, including the NLRP3 inflammasome, NF-kB, NFAT, GSK3β and VEGF, and discuss the involvement of P2X7R in chronic diseases. The possible therapeutic applications of P2X7R antagonists are also described.
损伤相关分子模式（DAMPs）是从感染或受伤细胞中释放出来的细胞内分子，可激活炎症和修复反应。最古老和最保守的 DAMPs 之一是细胞外 ATP，它主要通过激活 P2X7 受体（P2X7R）发挥其致炎作用。P2X7R 是一种 ATP 门控离子通道，大多数免疫细胞表达，包括单核细胞衍生的细胞谱系、T 和 B 淋巴细胞及其前体。在这里，我们概述了最近和已建立的文献中关于 P2X7R 在脓毒症和无菌性炎症中的作用。描述了 P2X7R 通过调节免疫反应来抑制细胞内细菌和寄生虫感染的能力，特别关注分枝杆菌和疟原虫。还简要介绍了关于 P2X7 在 HIV-1 等病毒感染中的作用的新兴文献。最后，我们描述了与 P2X7R 相关的许多与炎症相关的细胞内途径，包括 NLRP3 炎性体、NF-kB、NFAT、GSK3β 和 VEGF，并讨论了 P2X7R 在慢性疾病中的参与。还描述了 P2X7R 拮抗剂的可能治疗应用。
