The biology of nitric oxide and other reactive intermediates in systemic lupus erythematosus.
Formation of reactive nitrogen and oxygen intermediates (RNI and ROI) is an essential part of the innate immune response. Markers of systemic RNI production are increased in the setting of systemic lupus erythematosus (SLE) activity. Several lines of evidence suggest mechanisms through which the activity of inducible nitric oxide synthase (iNOS) is pathogenic in SLE, including the ability of peroxynitrite (ONOO(-), a product of iNOS activity) to modify proteins, lipids, and DNA. These modifications can alter enzyme activity and may increase the immunogenicity of self antigens, leading to a break in immune tolerance. In humans, observational data suggest that overexpression of iNOS and increased production of ONOO(-) lead to glomerular and vascular pathology. Therapies designed to target iNOS activity or scavenge ROI and RNI are in development and may provide the means to reduce the pathogenic consequences of ROI and RNI in SLE.
Oates
Jim C
JC
Department of Medicine, Division of Rheumatology, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 912, PO Box 250637, Charleston, SC 29425, USA. oatesjc@musc.edu
Gilkeson
Gary S
GS
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase