Current Concepts of Redox Signaling in the Lungs

Abstract

In the intracellular redox state (GSH/GSSG) the cell plays a key role in the regulation and potentiation of the inflammatory response in lung cells. Glutathione and thioredoxin are the important protective antioxidants in the lungs. Regulation of intracellular redox glutathione and thioredoxin levels in response to reactive oxygen/nitrogen species and in inflammation should have critical effects on different lung cells on the activation of redox sensor/signal transduction pathways and various transcription factors. Possibly via the modification of cysteine residues, oxidative stress activates multiple stress kinase pathways and transcription factors nuclear factor-kappaB and activator protein-1, which differentially regulate the genes for proinflammatory cytokines as well as the protective antioxidant genes. Emerging data suggest that protein-S-thiolation, protein-S-nitrosation, and oxidation of protein-SH (formation of sulfenic, sulfinic, and sulfonic acids) are critical in redox signaling during normal physiology and under oxidative stress in controlling the cellular processes. In this review, we discuss the recent findings in the context of redox signaling during inflammation, pathology, and the role of redox modulating agents/dietary interventions either to inhibit abnormal signaling or induce/boost the endogenous antioxidant systems. Furthermore, this also provides information as to how antioxidants are involved in redox signaling to control inflammatory and oxidative stress in the lung.

The Thioredoxin Reductase-1 Inhibitor Aurothioglucose Attenuates Lung Injury and Improves Survival in a Murine Model of Acute Respiratory Distress Syndrome

“…Inflammation causes enhanced reactive oxygen species (ROS) production and decreased GSH levels, resulting in upregulation of both pro-inflammatory and antioxidant genes (35). Transcription factors that regulate proinflammatory cytokines and chemokines are sensitive to GSH levels, and GSH depletion enhances pro-inflammatory signaling in the alveolar epithelium (19,36). Our data in LPS/ RA mice indicated that lung GSH levels were significantly decreased at 24 h of exposure (36 h after LPS administration) but recovered by 72 h (84 h after LPS administration).…”

Antioxidants as Potential Therapeutics for Lung Fibrosis

“…Oxidative stress is often defined as an imbalance between ROS production and antioxidant defenses. Oxidative stress can dysregulate cell signaling (158) and is a potential target for the development of therapeutics to treat lung fibrosis (110).…”

Interaction with CREB binding protein modulates the activities of Nrf2 and NF-κB in cystic fibrosis airway epithelial cells

“…Redox signaling pathways have been shown to play a key role in the activation of inflammatory cascades in the lung (37,44). For example, hydrogen peroxide (H 2 O 2 ) has been reported to mediate IL-1␤ (18) and TNF-␣ (8,20) receptor signaling cascades.…”