Therapeutic Effect of a Poly(ADP-Ribose) Polymerase-1 Inhibitor on Experimental Arthritis by Downregulating Inflammation and Th1 Response
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AutorGonzález-Rey, Elena; Martínez-Romero, Rubén; O'Valle, Francisco; Aguilar-Quesada, Rocío; Conde, Carmen; Delgado Mora, Mario; Oliver Pozo, Francisco Javier
Public Library of Science (PLOS)
ArthritisBone and joint mechanicsCartilageCytokinesInflammationInflammatory diseasesMacrophagesNeutrophils
González-Rey, E.; et al. Therapeutic Effect of a Poly(ADP-Ribose) Polymerase-1 Inhibitor on Experimental Arthritis by Downregulating Inflammation and Th1 Response. Plos One, 2(10): e1071 (2007). [http://hdl.handle.net/10481/30951]
PatrocinadorThis work has been supported by grants CTS870 from Junta de Andalucia to MD, SAF 2003-01217, RNIHG c03/02, PI050972, SAF2006-01089 and FIS G03/152 to FJO.
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.