Laudisi Federica, Sambucci Manolo, Pioli Claudio
ENEA (Italian Agency for New Technologies, Energy and Sustainable Economic Development), Laboratory of Radiation Biology and Biomedicine, Rome, Italy.
Endocr Metab Immune Disord Drug Targets. 2011 Dec;11(4):326-33. doi: 10.2174/187153011797881184.
Poly(ADP-ribose) polymerases (PARPs) represent a family of enzymes which synthesize and bind branched polymers of ADP-ribose to acceptor proteins using NAD as a substrate. PARP-1, the prototypical representative of the family, accounts for the majority of the poly(ADP-ribose) polymer synthesis. PARP-1 functions as a DNA nick sensor and signaling molecule binding to ssDNA and dsDNA protecting cells from genomic instability. PARP-1 activity plays a relevant role in the development of inflammatory responses largely contributing to tissue damage in ischemia/reperfusion conditions, such as stroke and myocardial infarction, and in septic shock. Recently, several findings revealed a wider immunological role for PARP-1. It regulates gene transcription in several types of immune cells, including dendritic cells, macrophages and lymphocytes. PARP-1 affects the stimulatory ability of dendritic cells, T cell activation and antibody production. Inhibition of PARP-1 enzymatic activity reduces the secretion of pro-inflammatory cytokines and ameliorates autoimmune diseases in several experimental models. Our recent findings showed that PARP-1 deficiency affects T cell differentiation rendering naïve CD4 T cells prone to differentiate in regulatory T cells. All together these findings show that PARP-1 plays a pivotal role in the balance between pro-inflammatory/effector and anti-inflammatory/regulatory responses, opening new possible therapeutic perspectives.
聚（ADP - 核糖）聚合酶（PARPs）是一类酶，它们以NAD为底物，合成并将ADP - 核糖的分支聚合物结合到受体蛋白上。该家族的典型代表PARP - 1负责大部分聚（ADP - 核糖）聚合物的合成。PARP - 1作为一种DNA切口传感器和信号分子，与单链DNA和双链DNA结合，保护细胞免受基因组不稳定的影响。PARP - 1的活性在炎症反应的发展中起相关作用，在很大程度上导致缺血/再灌注条件下的组织损伤，如中风和心肌梗死，以及脓毒症休克。最近，一些研究结果揭示了PARP - 1更广泛的免疫作用。它调节多种免疫细胞类型中的基因转录，包括树突状细胞、巨噬细胞和淋巴细胞。PARP - 1影响树突状细胞的刺激能力、T细胞活化和抗体产生。在几种实验模型中，抑制PARP - 1的酶活性可减少促炎细胞因子的分泌并改善自身免疫性疾病。我们最近的研究结果表明，PARP - 1缺乏会影响T细胞分化，使初始CD4 T细胞易于分化为调节性T细胞。所有这些研究结果表明，PARP - 1在促炎/效应和抗炎/调节反应之间的平衡中起关键作用，开辟了新的可能治疗前景。
