1. Introduction
Thioredoxin (Trx) is a ubiquitously expressed protein with a low
molecular weight of 12 kDa; it composes the Trx system with NADPH and
Trx reductase (TrxR).1 Trx has thiol-disulphide
reductase activity that is affected by a highly conserved active site
(-Cys32-Gly-Pro-Cys35-).2The reduced form of Trx transfers reducing equivalents to disulphides
within the target molecules and catalyses their reduction. In this
process, TrxR uses NADPH to reduce the active site disulphide to a
dithiol in the Trx substrates3 (Figure 1a). Overall,
the Trx system plays a critical role in regulating cellular redox
balance through the reversible thiol-disulphide exchange reaction.
Trx1 is a major Trx isoform located in the cytoplasm that also
translocates to the nucleus; it can directly scavenge reactive oxygen
species (ROS) and thereby protects against oxidative
stress.4In addition, Trx1 is involved in various redox-dependent cellular
processes such as gene expression, signal transduction, cell growth and
apoptosis, and it interacts with various target
molecules.5 Under stress conditions, Trx1 is released
into the extracellular space where it exerts a cytoprotective effect and
has cytokine-like activities.6
Allergic diseases comprise a group of immune-mediated disorders that are
mainly characterised by a Th2 immune response phenotype. In asthmatic
patients in the attack stage, plasma Trx1 levels were found to be
significantly higher than that those in the remission stage, and the
level of Trx1 was substantially increased as the severity of the asthma
attack increased.7 This suggests that Trx1 could be a
useful clinical parameter with which to predict the progression of
asthma.
The protective effects of Trx1 have been determined in relation to the
pathogenesis of many human disorders including metabolic syndrome, and
neurodegenerative, cardiovascular and inflammatory
diseases.8-11 In this review, we focus on the findings
of recent research into the underlying intercellular and intracellular
mechanisms by which Trx1 regulates immune cells in response to allergic
inflammatory diseases, such as allergic asthma, food and drug allergies,
contact dermatitis and allergic rhinitis, as well as potential Trx-based
therapeutic strategies for treatment of allergic diseases.