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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.
AuthorsFederica Laudisi, Manolo Sambucci, Claudio Pioli
JournalEndocrine, metabolic & immune disorders drug targets (Endocr Metab Immune Disord Drug Targets) Vol. 11 Issue 4 Pg. 326-33 (Dec 2011) ISSN: 2212-3873 [Electronic] United Arab Emirates
PMID21476963 (Publication Type: Journal Article, Review)
Chemical References
  • Anti-Inflammatory Agents, Non-Steroidal
  • Inflammation Mediators
  • Poly(ADP-ribose) Polymerase Inhibitors
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
Topics
  • Adaptive Immunity (immunology)
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal (pharmacology, therapeutic use)
  • Humans
  • Immune System Diseases (immunology, pathology, therapy)
  • Inflammation Mediators (physiology, therapeutic use)
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly(ADP-ribose) Polymerases (physiology)

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