Inflammation, Immunity and Redox Signaling

Abstract

It has long been known that several types of antioxidants also possess anti-inflammatory properties indicating a strong relationship between inflammation and oxidative stress. Reactive oxygen species (ROS) generated by inflammatory cells not only help to kill pathogens but also act on the inflammatory cells themselves, altering the intracellular redox balance and functioning as signaling molecules involved with the regulation of inflammatory and immunomodulatory genes. Indeed, at the transcriptional level, ROS play a key role in the control of nuclear factor kappa B (NF-B), activator protein-1 (AP-1), and other transcription factors involved in gene expression of both inflammatory and immune mediators. More interestingly, ROS and also reactive nitrogen species (RNS) can either activate or inactivate these transcription factors by chemically modifying critical amino acid residues within these proteins or on residues of accessory proteins of the respective signaling pathways. The interest in the molecular mechanisms involved in redox regulation of inflammatory and immune responses has gone beyond the transcription factors as target proteins. Proteins involved in signaling cascades that ultimately culminate in the production of inflammatory and immune mediators have been investigated as redox sensors and therefore targets for ROS and or RNS modulation. For instance, NLRP3 inflammasome is a cysteine-rich multidimeric protein that participates in the formation of a molecular platform for caspase1-dependent IL-1 secretion. It has been suggested that IL-1 production and secretion in monocytes is a redox regulated event. However, the mechanisms of production and the nature of ROS involved in inflammasome activation are still unknown. This chapter will discuss some of the latest concepts on how ROS and RNS can modulate the inflammatory and immune responses at the molecular level, from redox regulated transcription factors to redox sensitive proteins involved in inflammatory and immune signaling pathways.