磷脂酰肌醇3-激酶γ/δ与炎症相关疾病

磷脂酰肌醇3-激酶(PI3K)是一类脂质与蛋白激酶家族,其主要通过在磷脂酰肌醇的肌醇环三位进行磷酸化产生胞内重要的第二信使——磷脂酰肌醇-3,4,5-三磷酸(phosphatidyl inositol 3,4,5-trisphosphate,PIP3)而发挥作用.磷脂酰肌醇3-激酶γ/δ(PI3Kγ/δ)是I类PI3K家族中的成员,其主要表达于免疫相关细胞中,这2种PI3K亚型参与先天性与获得性免疫应答.因此,PI3Kγ/PI3Kδ被视为因免疫反应调控异常导致的炎症疾病的治疗药物靶点.目前,利用特异性抑制剂靶向干预PI3Kγ和/或PI3Kδ,成为炎症相关疾病治疗的新策略.本文简介了PI3Kγ与PI3Kδ在不同类型免疫细胞中的功能;并就采用小分子特异性抑制剂,靶向抑制PI3Kγ和/或PI3Kδ在各类炎症相关疾病中的治疗作用和效果进行综述.

Phosphatidylinositol 3-Kinase γ/δ in Inflammatory Diseases

PI3Ks are a family of lipid and protein kinases which produce an important secondary messenger PIP3 by phosphorylating phosphoinositide on D3 position of the inositol ring. PI3Kγ and PI3Kδ belong to the Class I PI3Ks which are mainly expressed in immune cells. These two isoforms of PI3Ks play an essential role in the innate and acquired immune responses. Therefore, PI3Kγ and PI3Kδ are considered as the effective therapeutic target for the inflammatory diseases intervention. Currently, the pharmacological targeting of PI3Kγ and/or PI3Kδ and the development of novel isoform-selective PI3K inhibitor drugs offers one of the most promising strategies for the treatment of inflammatory diseases. This review provided a brief introduction of PI3Kγ/δ functions in distinct immune cell types (leukocyte, macrophage and lymphocyte etc.) and the latest progress of the therapeutic effect of various inflammatory diseases (autoimmune diseases, respiratory diseases, cardiovascular diseases and systemic inflammatory diseases, etc.) by selective targeting PI3Kγ and/or PI3Kδ with small molecules.