Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
School of Pharmacy, University of Camerino, Camerino, Italy.
Immunity. 2017 Jul 18;47(1):15-31. doi: 10.1016/j.immuni.2017.06.020.
Adenosine triphosphate (ATP) accumulates at sites of tissue injury and inflammation. Effects of extracellular ATP are mediated by plasma membrane receptors named P2 receptors (P2Rs). The P2R most involved in inflammation and immunity is the P2X7 receptor (P2X7R), expressed by virtually all cells of innate and adaptive immunity. P2X7R mediates NLRP3 inflammasome activation, cytokine and chemokine release, T lymphocyte survival and differentiation, transcription factor activation, and cell death. Ten human P2RX7 gene splice variants and several SNPs that produce complex haplotypes are known. The P2X7R is a potent stimulant of inflammation and immunity and a promoter of cancer cell growth. This makes P2X7R an appealing target for anti-inflammatory and anti-cancer therapy. However, an in-depth knowledge of its structure and of the associated signal transduction mechanisms is needed for an effective therapeutic development.
三磷酸腺苷(ATP)在组织损伤和炎症部位积累。细胞外 ATP 的作用是通过被称为 P2 受体(P2Rs)的质膜受体介导的。在炎症和免疫中最相关的 P2R 是 P2X7 受体(P2X7R),它几乎表达于先天和适应性免疫的所有细胞。P2X7R 介导 NLRP3 炎性体激活、细胞因子和趋化因子释放、T 淋巴细胞存活和分化、转录因子激活和细胞死亡。已知有 10 个人类 P2RX7 基因剪接变体和几个产生复杂单倍型的 SNP。P2X7R 是炎症和免疫的有效刺激物,也是促进癌细胞生长的因素。这使得 P2X7R 成为抗炎和抗癌治疗的一个有吸引力的靶点。然而,为了有效的治疗开发,需要对其结构和相关信号转导机制有深入的了解。