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.
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Authors | Federica Laudisi, Manolo Sambucci, Claudio Pioli |
Journal | Endocrine, 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 |
PMID | 21476963
(Publication Type: Journal Article, Review)
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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
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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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