Therapeutic effect of a poly(ADP-ribose) polymerase-1 inhibitor on experimental arthritis by downregulating inflammation and Th1 response.
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| Abstract |
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 | Elena Gonzalez-Rey, Ruben Martínez-Romero, Francisco O'Valle, Rocío Aguilar-Quesada, Carmen Conde, Mario Delgado, F Javier Oliver |
| Journal | PloS one (PLoS One) Vol. 2 Issue 10 Pg. e1071 (Oct 31 2007) ISSN: 1932-6203 [Electronic] United States |
| PMID | 17971849 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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