Poly (ADP-Ribose) Polymerase-1 (PARP-1) as Immune Regulator

Author(s): Federica Laudisi, Manolo Sambucci, Claudio Pioli.

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets
(Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders)

Volume 11 , Issue 4 , 2011

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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.

Keywords: adaptive immunity, immune-mediated diseases, inflammation, PARP-1, polymerases, DNA, therapeutic perspectives, Inhibition, lymphocytes, genomic instability, enzymatic, pro-inflammatory

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Article Details

VOLUME: 11
ISSUE: 4
Year: 2011
Page: [326 - 333]
Pages: 8
DOI: 10.2174/187153011797881184
Price: $65

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