The role of iNOS in chronic inflammatory processes in vivo: is it damage-promoting, protective, or active at all?
The expression of the inducible nitric oxide synthase (iNOS) is one of the direct consequences of an inflammatory process. Early studies have focused on the potential toxicity of the ensuing high-output NO-synthesis serving as a means to eliminate pathogens or tumor cells but also contributing to local tissue destruction during chronic inflammation. More recently, however, data are accumulating on a protective effect of high-output NO synthesis and - equally important - on a gene-regulatory function that helps to mount a protective stress response and simultaneously aids in down-regulating the proinflammatory response. These findings appear to contrast to the often observed sustained iNOS-expression during chronic inflammatory diseases, as for instance in Psoriasis vulgaris and other conditions with a chronic Th1-like reactivity. We here pose the question as to whether the iNOS is really active in these diseases. We review the data accumulated on iNOS expression in chronic diseases. We also report on the various factors that potentially interfere with proper NO formation by the expressed enzyme. We also highlight the recent findings of how, why and where evidences emerge that impeded NO formation contributes to chronic disease processes and finally present details on our current understanding of such abnormally low NO synthesis and its contribution to the pathophysiological processes of the human proinflammatory skin disease Psoriasis vulgaris.
Suschek
Christoph V
CV
Department of Immunobiology, Heinrich-Heine-University Düsseldorf, P.O. Box 101007, D-40001 Düsseldorf, Germany.
Schnorr
Oliver
O
Kolb-Bachofen
Victoria
V
D000818:Animals; D001119:Arginase / Q000378:metabolism; D001120:Arginine / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D003067:Coenzymes / Q000378:metabolism; D006801:Humans; D007154:Immune System Diseases / Q000201:enzymology; D007249:Inflammation / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D011565:Psoriasis / Q000201:enzymology / Q000473:pathology
D003067:Coenzymes; D009569:Nitric Oxide; D001120:Arginine; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D001119:Arginase