Regulation of nitrogen monoxide production in human malaria.

The production of nitrogen monoxide (NO.) contributes to defence mechanisms of the immune system to fight infectious agents like bacteria and protozoa. The respective gene producing the NO. has to be carefully regulated so that an overwhelming response kills the pathogen but does not harm the host. A strong increase in the NO. production for efficient anti-microbial activity is achieved by the transcriptional up-regulation of the nitric oxide synthase 2 gene (NOS2 or inducible nitric oxide synthase, iNOS), which is regulated by a number of transcription factors that are vital in the regulation of many genes involved in the immune response. Binding sites for members of the nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP1) families have been detected and seem to fulfil their function in vitro. Genetic variants of the iNOS genes have been identified that are linked to NO. production and to the outcome of malaria in humans.