Document Detail


Therapeutic effect of a poly(ADP-ribose) polymerase-1 inhibitor on experimental arthritis by downregulating inflammation and Th1 response.
MedLine Citation:
PMID:  17971849     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Poly(ADP-ribose) polymerase-1 (PARP-1) synthesizes and transfers ADP ribose polymers to target proteins, and regulates DNA repair and genomic integrity maintenance. PARP-1 also plays a crucial role in the progression of the inflammatory response, and its inhibition confers protection in several models of inflammatory disorders. Here, we investigate the impact of a selective PARP-1 inhibitor in experimental arthritis. PARP-1 inhibition with 5-aminoisoquinolinone (AIQ) significantly reduces incidence and severity of established collagen-induced arthritis, completely abrogating joint swelling and destruction of cartilage and bone. The therapeutic effect of AIQ is associated with a striking reduction of the two deleterious components of the disease, i.e. the Th1-driven autoimmune and inflammatory responses. AIQ downregulates the production of various inflammatory cytokines and chemokines, decreases the antigen-specific Th1-cell expansion, and induces the production of the anti-inflammatory cytokine IL-10. Our results provide evidence of the contribution of PARP-1 to the progression of arthritis and identify this protein as a potential therapeutic target for the treatment of rheumatoid arthritis.
Authors:
Elena Gonzalez-Rey; Ruben Martínez-Romero; Francisco O'Valle; Rocío Aguilar-Quesada; Carmen Conde; Mario Delgado; F Javier Oliver
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-10-31
Journal Detail:
Title:  PloS one     Volume:  2     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2007  
Date Detail:
Created Date:  2007-10-31     Completed Date:  2008-07-15     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e1071     Citation Subset:  IM    
Affiliation:
Institute of Parasitology and Biomedicine, Consejo Superior de Investigaciones Científicas, Granada, Spain.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arthritis, Experimental / therapy
Arthritis, Rheumatoid / therapy*
Autoimmune Diseases / immunology
Cytokines / metabolism
Down-Regulation*
Enzyme Inhibitors / pharmacology*
Inflammation
Isoquinolines / pharmacology
Mice
Models, Biological
Poly(ADP-ribose) Polymerases / antagonists & inhibitors,  metabolism*
Polymers / chemistry
T-Lymphocytes / metabolism
Th1 Cells / cytology*,  immunology
Chemical
Reg. No./Substance:
0/5-aminoisoquinolinone; 0/Cytokines; 0/Enzyme Inhibitors; 0/Isoquinolines; 0/Polymers; EC 2.4.2.30/Poly(ADP-ribose) Polymerases
Comments/Corrections

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