Inducible nitric oxide synthase in human diseases

Extract

INTRODUCTION

Since its discovery as a biologically active molecule in the late 1980s, nitric oxide (NO) has been found to play an important role as signal molecule in many parts of the organism as well as cytotoxic or regulatory effector molecule of the innate immune response. The signal molecule NO is synthesized on demand for short periods of time (seconds to minutes) following enzyme activation of constitutively expressed endothelial NO synthase (eNOS) or neuronal NO synthase (nNOS). In contrast, the inducible NO synthase (iNOS) is expressed after cell activation only and then produces NO for comparatively long periods of time (hours to days). Thus, regulated short pulsative synthesis versus constant NO production differentiates between physiological and pathophysiological actions of NO (for review see [1]). As human monocytes in contrast to rodent ones do not produce large amounts of NO when activated in vitro, iNOS expression in human diseases has long been questionable. However, in the last 3 years data have accumulated on iNOS expression in a variety of human diseases or disorders. We here try to review our current understanding of the role of iNOS in human diseases.