Molecular mechanisms regulating iNOS expression in various cell types.

Abstract

Inducible nitric oxide synthase (iNOS) has been shown to be present in a variety of cell types, and nitric oxide (NO) has been implicated in a multitude of biological functions. The purpose of this review is twofold: (1) to provide a comprehensive table of cell types that produce NO together with the effects of agents used to study iNOS regulation, as a ready reference for the investigators in the field; and (2) to summarize recent observations dealing with iNOS signal transduction mechanisms. Initially, the major regulation of NO production was believed to occur at the transcription step, but now it is recognized that NO regulation can occur at the transcriptional, posttranscriptional, translational, and posttranslational level. There have been a number of studies of the regulation of iNOS in various cell types, often yielding conflicting results. The major emphasis of this review is on iNOS signal transduction mechanisms. For example, the role of JAK kinases and mitogen-activated protein (MAP) kinases in iNOS regulation is elaborated. In addition, species differences in the iNOS promoter region and the role of RNA structure in iNOS expression is discussed. The role MAP kinases play in translational regulation in addition to transcriptional regulation is emphasized. An analysis of the current data and suggestions for future studies are also presented.