What sense lies in antisense inhibition of inducible nitric oxide synthase expression?
The impact of nitric oxide (NO) synthesized after activation by proinflammatory cytokines and/or bacterial products by an inducible NO synthase (iNOS) is still contradictory. Expression of iNOS in inflammatory reactions is often found predominantly in cells of epithelial origin, and in these cases NO may serve as a protective agent limiting pathogen spreading, downregulating local inflammatory reactions by inducing production of Th2-like responses in a classical feedback circle, or limiting tissue damage during stress conditions. However, an abundant amount of data on chronic human disorders with predominant proinflammatory Th1-like reactions points to a destructive role of iNOS activity calling for a specific inhibition. Various methods to inhibit iNOS have been established to elucidate a protective versus a destructive role of NO during various stresses. In this review, we focus on antisense (AS)-mediated gene knock-down as a relatively new method to inhibit NO production and summarize the techniques applied and their successes. At least in theory, it provides a specific, rapid, and potentially high-throughput method for inhibiting gene expression and function. We here discuss the opportunities of iNOS-directed AS-ODN, and extensively deal with limitations and experimental problems.
Hemmrich
Karsten
K
Research Group Immunobiology, MED-Heinrich-Heine-University of Düsseldorf, Gebäude 23.12, Postfach 10 10 07, D-40001 Düsseldorf, Germany. hemmrich@gmx.de
Kröncke
Klaus-D
KD
Suschek
Christoph V
CV
Kolb-Bachofen
Victoria
V
D000818:Animals; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D016376:Oligonucleotides, Antisense; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II