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Título

Therapeutic effect of a poly(ADP-ribose) polymerase-1 inhibitor on experimental arthritis by downregulating inflammation and Th1 response

Autor González-Rey, Elena; Martínez-Romero, Rubén; O'Valle, Francisco; Aguilar-Quesada, Rocío; Conde, Carmen; Delgado, M.; Oliver, Francisco Javier
Fecha de publicación 31-oct-2007
EditorPublic Library of Science
Citación PLoS ONE 2(10): e1071
ResumenPoly(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.
Descripción 6 páginas, 3 figuras.-- PMID: 17971849 [PubMed].-- PMCID: PMC2034533.
Versión del editorhttp://dx.doi.org/10.1371/journal.pone.0001071
URI http://hdl.handle.net/10261/9835
DOI10.1371/journal.pone.0001071
ISSN1932-6203 (Online)
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