Nitric oxide, chronic inflammation and autoimmunity.
Whilst many physiological functions of nitric oxide (NO) have been revealed so far, recent evidence proposes an essential role for NO in T lymphocyte activation and signal transduction. NO acts as a second messenger, activating soluble guanyl cyclase and participating in signal transduction pathways involving cyclic GMP. NO modulates mitochondrial events that are involved in apoptosis and regulates mitochondrial biogenesis in many cell types, including lymphocytes. Several studies undertaken on patients with RA and SLE have documented increased endogenous NO synthesis, although the effects of NO may be distinct. Here, we discuss recent evidence that NO contributes to T cell dysfunction in both SLE and RA by altering multiple signaling pathways in T cells. Although NO may play a physiological role in lymphocyte cell signaling, its overproduction may perturb T cell activation, differentiation and effector responses, each of which may contribute in different ways to the pathogenesis of autoimmunity.
Nagy
György
G
Department of Rheumatology, Semmelweis University, Medical School, Arpád fejedelem u.7, 1023 Budapest, Hungary. gyorgyngy@gmail.com
Clark
Joanna M
JM
Buzás
Edit I
EI
Gorman
Claire L
CL
Cope
Andrew P
AP
D001172:Arthritis, Rheumatoid / Q000276:immunology; D015551:Autoimmunity; D006801:Humans; D007249:Inflammation; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D009569:Nitric Oxide