| Therapeutic effect of a poly(ADP-ribose) polymerase-1 inhibitor on experimental arthritis by downregulating inflammation and Th1 response. | |
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MedLine Citation:
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PMID: 17971849 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-10-31 |
Journal Detail:
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Title: PloS one Volume: 2 ISSN: 1932-6203 ISO Abbreviation: PLoS ONE Publication Date: 2007 |
Date Detail:
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Created Date: 2007-10-31 Completed Date: 2008-07-15 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 101285081 Medline TA: PLoS One Country: United States |
Other Details:
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Languages: eng Pagination: e1071 Citation Subset: IM |
Affiliation:
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Institute of Parasitology and Biomedicine, Consejo Superior de Investigaciones Científicas, Granada, Spain. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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