PARP-1: a new player in the asthma field?
PARP-1: a new player in the asthma field?
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PARP-1：哮喘领域的新参与者？
DOI：
10.1111/j.1398-9995.2011.02551.x
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发表时间：
2011
期刊：
影响因子：
12.4
通讯作者：
Virág,L
中科院分区：
文献类型：
--
作者：
Szabó,É;Kovács,I;Grune,T;Haczku,A;Virág,L
哮喘的呼吸道炎症由一个复杂的细胞因子网络调节(1)。其中，白介素4和白介素5被认为是维持Th2型免疫反应的核心角色。IL-4以一种自分泌的方式调节Th2淋巴细胞的扩张和激活，Th2淋巴细胞是CD4+T辅助细胞的一个亚群。IL-4还刺激IL-5的表达，IL-5是一种专门负责炎症组织中嗜酸粒细胞分化、激活和存活的细胞因子。尽管它们的确切作用仍有争议，但嗜酸性粒细胞被认为在过敏性炎症和哮喘中具有重要的致病作用。因此，这一途径的有效靶向在过去20年里一直是深入研究的主题。IL-4驱动的信号通路已经被很好地映射：当IL-4与IL-4受体结合时，IL-4激活受体相关的激酶JAK-1和JAK-3(图1A)。JAK-1和JAK-3对STAT-6的酪氨酸磷酸化诱导STAT-6的二聚化和核移位(图1B)。STAT-6然后激活一些致炎基因的转录(图1C)，包括GATA-3(GATA结合蛋白-3)的转录，GATA-3是IL-5表达的主要转录调节因子[在(1)中回顾]。Datta等人(2)在本期《过敏》杂志上报道，核蛋白PARP-1[聚(ADP-核糖)聚合酶-1]是IL-4驱动的导致IL-5表达的信号通路的一种新的调节因子。他们提出了一种作用机制，通过PARP-1介导的STAT-6蛋白的稳定来增强GATA-3的表达(图1D)。
The asthmatic airway inflammation is regulated by an elaborate network of cytokines (1). Among these, interleukin (IL)-4 and IL-5 are thought to be central players in perpetuating a Th2-type immune response. In an autocrine fashion, IL-4 regulates the expansion and activation of Th2 lymphocytes, a subset of CD4+ T helper cells. IL-4 also stimulates the expression of IL-5, the cytokine specifically responsible for differentiation, activation and survival of eosinophil granulocytes in the inflamed tissue. Although their exact role is still subject to debate, eosinophils have been regarded to have a major pathogenic importance in allergic inflammation and asthma. Effective targeting of this pathway has been therefore the subject of intensive research in the past two decades. The IL-4-driven signaling pathway has been well mapped: upon binding to the IL-4 receptor, IL-4 activates the receptor-associated kinases JAK-1 and JAK-3 (Fig. 1A). Tyrosine phosphorylation of STAT-6 by JAK-1 and JAK-3 induces dimerization and nuclear translocation of STAT-6 (Fig. 1B). STAT-6 then activates transcription of a number of proinflammatory genes (Fig. 1C) including that of GATA-3 (GATA binding protein-3), a master transcriptional regulator of IL-5 expression [reviewed in (1)]. Datta et al.(2) reported in this issue of Allergy that the nuclear protein PARP-1 [poly (ADP-ribose) polymerase-1] is a novel regulator of the IL-4-driven signaling pathway leading to IL-5 expression. They proposed a mechanism of action through enhancement of GATA-3 expression by PARP-1 mediated stabilization of STAT-6 protein (Fig. 1D).