Partial protection against collagen antibody-induced arthritis in PARP-1 deficient mice.
Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear DNA-binding protein that participates in the regulation of DNA repair and maintenance of genomic integrity. In addition, PARP-1 has a role in several models of inflammation disease, where its absence or inactivation confers protection. The aim of this study was to analyze the impact of selective PARP-1 suppression in collagen antibody-induced arthritis. We show that PARP-1 deficiency partially reduces the severity of arthritis, although the incidence of disease was similar in control and deficient mice. Decreased clinical scores were accompanied by partial reduction of histopathological findings. Interestingly, quantitative real-time PCR and ELISA analysis revealed that the absence of PARP-1 down-regulated IL-1beta and monocyte chemotactic protein 1 expression in arthritic joints whereas tumor necrosis factor-alpha transcription was not impaired. 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.
García
Samuel
S
Research Laboratory, Hospital Clínico Universitario, Choupana s/n, 15706-Santiago de Compostela, Spain. samugp13@yahoo.es
Bodaño
Ana
A
González
Antonio
A
Forteza
Jerónimo
J
Gómez-Reino
Juan J
JJ
Conde
Carmen
C
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D001172:Arthritis, Rheumatoid / Q000628:therapy; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D006614:Hindlimb; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000172:deficiency* / Q000235:genetics; D012016:Reference Values; D013583:Synovial Membrane / Q000276:immunology / Q000503:physiopathology
C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases