The Role of Poly(ADP-ribose) Polymerase-1 in Rheumatoid Arthritis

Abstract

Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme with a crucial role in the maintenance of genomic stability. In addition to the role of PARP-1 in DNA repair, multiple studies have also demonstrated its involvement in several inflammatory diseases, such as septic shock, asthma, atherosclerosis, and stroke, as well as in cancer. In these diseases, the pharmacological inhibition of PARP-1 has shown a beneficial effect, suggesting that PARP-1 regulates their inflammatory processes. In recent years, we have studied the role of PARP-1 in rheumatoid arthritis, as have other researchers, and the results have shown that PARP-1 has an important function in the development of this disease. This review summarizes current knowledge on the effects of PARP-1 in rheumatoid arthritis.

Figure 1

Effect of PARP-1 on the TNF-α induced production of inflammatory mediators in RA FLS. TNF-α stimulation induces the activation and the translocation to the nucleus of the transcription factors NF-κB and AP-1. In the nucleus, PARP-1 enzymatic activity and/or direct protein interaction enhances the transcriptional activity of both NF-κB and AP-1, leading to the production of inflammatory mediators.