Oxidative Stress in Inflammation

Oxidative stress (OS) is increasingly recognized as a major upstream component in the signaling cascade involved in the inflammatory response due to its capacity to stimulate the expression of adhesion molecules and the production of chemoattractant agents. Several components of the signaling pathways that sense oxidative and inflammatory injury have recently been identified in cells. Certain stress-activated inflammasomes, protein kinases, and upstream signaling enzymes can activate redox-sensitive transcription factors (e.g., NF-κB), thereby upregulating the expression of early-response genes to adapt and survive the subsequent injury. Oxidative damage appears to play a central role in the development of a wide range of diseases including acute and chronic inflammatory diseases, allergic and auto-immune diseases, as well as aging process, to name just a few. In addition, transient changes in the redox status, communicated via series of signaling systems, initiate de novo synthesis of a distinct set of cytoprotective or stress-responsive proteins and enzymes that are responsible for adaptive cellular responses to pathogen invasion. Furthermore, reactive species (RS) are important factors involved in multiple sequences of biomolecular reactions that lead to wound repair and healing. This chapter examines the role of OS in the inflammatory response and reviews the available data on cell sources of RS during this process. It shows the effect of pro-oxidants and antioxidants as inflammatory mediators in signaling pathways acting from the initial stimulus to termination. It also examines how oxidative events and inflammatory responses affect each other and give a thorough account of free radicals (FR) as mediators of inflammation. Molecular details on redox signaling and on the function of redox master switches are elucidated.