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.