Extracellular thioredoxin levels are increased in patients with acute lung injury

Abstract

Background: Acute lung injury (ALI) and its extreme manifestation the acute respiratory distress syndrome (ARDS) complicate a wide variety of serious medical and surgical conditions. Thioredoxin is a small ubiquitous thiol protein with redox/inflammation modulatory properties relevant to the pathogenesis of ALI. We therefore investigated whether thioredoxin is raised extracellulary in patients with ALI and whether the extent of any increase is dependent upon the nature of the precipitating insult. Methods: Bronchoalveolar lavage (BAL) fluid and plasma samples were collected from patients with ALI (n = 30) and healthy controls (n = 18, plasma; n = 14, BAL fluid). Lung tissue was harvested from a separate group of patients and controls (n = 10). Thioredoxin was measured by ELISA in fluids and by immunohistochemistry in tissue. Interleukin (IL)-8 levels were determined by ELISA. Disease severity was assessed as APACHE II and SOFA scores. Results: BAL fluid levels of thioredoxin were higher in patients with ALI than in controls (median 61.6 ng/ ml (IQR 34.9-132.9) v 16.0 ng/ml (IQR 8.9-25.1), p,0.0001); plasma levels were also significantly higher. When compared with controls, sections of wax embedded lung tissue from patients with ALI showed greater positive staining for thioredoxin in alveolar macrophages and type II epithelial cells. BAL fluid levels of thioredoxin correlated with IL-8 levels in BAL fluid but not with severity of illness scores or mortality. BAL fluid levels of thioredoxin, IL-8, and neutrophils were significantly greater in patients with ALI of pulmonary origin. Conclusions: Extracellular thioredoxin levels are raised in patients with ALI, particularly of pulmonary origin, and have a significant positive association with IL-8. Extracellular thioredoxin levels could provide a useful indication of inflammation in ALI.

Protection from Lipopolysaccharide-induced Lung Injury by Augmentation of Airway S-Nitrosothiols

“…Another possible mediator of airway SNO depletion in our model is thioredoxin, which has been shown to regulate protein denitrosylation (29). Although airway thioredoxin was not quantified in this study, airway fluid thioredoxin levels are known to be increased in patients with ALI (30).…”

Redox-based regulation of signal transduction: Principles, pitfalls, and promises

“…Intriguingly, following certain stimuli, Trx1 can also be translocated to the nucleus [90], or to the extracellular compartment following leaderless export [91]. Circulating levels of Trx were reported to be increased in patients with heart disease, rheumatoid arthritis, acute lung injury, or HIV infection, and showed various associations with severity of disease [92][93][94][95]. Extracellular Trx can act as a unique chemoattractant for neutrophils, monocytes, and T cells [96].…”

Redox-Active Protein Thioredoxin-1 Administration Ameliorates Influenza A Virus (H1N1)-Induced Acute Lung Injury in Mice

“…The effects of a well-known glutathione precursor, N-acetylcysteine were elevated in many oxidative and inflammatory disorders (27)(28)(29)(30), plasma TRX-1 concentrations were persistently low in children with meningococcal septic shock, possibly because of a genetic predisposition (46). Plasma TRX-1 concentrations were lower in patients with neutropenia/sepsis than in patients with systemic inflammatory response syndrome/sepsis (47).…”

“…Furthermore, TRX-1 suppresses inflammation by regulating neutrophil activation and extravasation and exerts the anti-inflammatory effect (15,16). In the clinical field, extracellular concentrations of TRX-1 have been measured in various conditions characterized by oxidative stress and inflammation, including sepsis, viral infection, autoimmune disease, ischemia-reperfusion injury, and acute lung injury (27)(28)(29)(30). These studies document that the TRX-1 concentrations are elevated in patients with these diseases and that they are correlated significantly with the activity of such diseases.…”