Aberrant reactive oxygen and nitrogen species generation in rheumatoid arthritis (RA): causes and consequences for immune function, cell survival, and therapeutic intervention

Darren Charles Phillips, H K Irundika Dias, George D. Kitas, Helen R Griffiths

Research output: Contribution to journalArticle

Abstract

The infiltration and persistence of hematopoietic immune cells within the rheumatoid arthritis (RA) joint results in elevated levels of pro-inflammatory cytokines, increased reactive oxygen (ROS) and -nitrogen (RNS) species generation, that feeds a continuous self-perpetuating cycle of inflammation and destruction. Meanwhile, the controlled production of ROS is required for signaling within the normal physiological reaction to perceived "foreign matter" and for effective apoptosis. This review focuses on the signaling pathways responsible for the induction of the normal immune response and the contribution of ROS to this process. Evidence for defects in the ability of immune cells in RA to regulate the generation of ROS and the consequence for their immune function and for RA progression is considered. As the hypercellularity of the rheumatoid joint and the associated persistence of hematopoietic cells within the rheumatoid joint are symptomatic of unresponsiveness to apoptotic stimuli, the role of apoptotic signaling proteins (specifically Bcl-2 family members and the tumor suppressor p53) as regulators of ROS generation and apoptosis are considered, evaluating evidence for their aberrant expression and function in RA. We postulate that ROS generation is required for effective therapeutic intervention.
Original languageEnglish
Pages (from-to)743-85
Number of pages43
JournalAntioxidants and Redox Signaling
Volume12
Issue number6
Early online date17 Jan 2010
DOIs
Publication statusPublished - 28 Feb 2010

Keywords

  • animals
  • rheumatoid arthritis
  • cell survival
  • humans
  • reactive nitrogen species
  • reactive oxygen species

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