TY - JOUR
T1 - Aberrant reactive oxygen and nitrogen species generation in rheumatoid arthritis (RA)
T2 - causes and consequences for immune function, cell survival, and therapeutic intervention
AU - Phillips, Darren Charles
AU - Dias, H K Irundika
AU - Kitas, George D.
AU - Griffiths, Helen R
PY - 2010/2/28
Y1 - 2010/2/28
N2 - 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.
AB - 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.
KW - animals
KW - rheumatoid arthritis
KW - cell survival
KW - humans
KW - reactive nitrogen species
KW - reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=77649260574&partnerID=8YFLogxK
UR - http://online.liebertpub.com/doi/abs/10.1089/ars.2009.2607
U2 - 10.1089/ars.2009.2607
DO - 10.1089/ars.2009.2607
M3 - Article
C2 - 19686039
SN - 1557-7716
VL - 12
SP - 743
EP - 785
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
IS - 6
ER -