title: Poly (ADP-ribose) polymerase-1 (PARP-1) as immune regulator.
abstract: 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.
authors.affiliation: ENEA (Italian Agency for New Technologies, Energy and Sustainable Economic Development), Laboratory of Radiation Biology and Biomedicine, Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Laudisi
authors.forename: Manolo
authors.initials: M
authors.lastname: Sambucci
authors.forename: Claudio
authors.initials: C
authors.lastname: Pioli
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007154:Immune System Diseases / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D018836:Inflammation Mediators / Q000502:physiology* / Q000627:therapeutic use; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018836:Inflammation Mediators; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases