Effects of thioredoxin on established airway remodeling in a chronic antigen exposure asthma model

Thioredoxin suppresses airway inflammation independently of systemic Th1/Th2 immune modulation

“…Nevertheless, it is noteworthy that administration of TRX during allergen-challenging phase, but not allergen-sensitization phase, suppressed airway inflammation, indicating that TRX could suppress Th2-driven inflammation irrespectively of initial development of Th2 immunity [23]. When all of the data are considered together, there are a number of studies that demonstrated a protective role for endogenous and/or exogenous TRX in different models of inflammatory diseases including autoimmune myocarditis [34], diabetes [18,35], gastritis [36], colitis [32] as well as asthma [23,37]. Thus, it seems unlikely that the sole function of TRX to negatively regulate inflammatory reactions is mediated through the modulation of Th1/Th2 immunity.…”

Influence of Histamine H1 Receptor Antagonists on Thioredoxin Production In vitro and In vivo

“…It is reported that TRX suppressed the CC chemokine-induced chemotaxis of eosinophils through inhibition of both activation of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase pathways [22], which play an important role in eosinophil chemotaxis [23]. Treatment of mice with TRX prevents the establishment of airway inflammation and overproduction of macrophage inflammatory protein (MIP)-1, RANTES, IL-4 and IL-5, which are involved in the pathogenesis of allergic inflammation, in chronic antigen exposure mice [11,12]. Furthermore, it is also reported that airway remodeling and eosinophilic inflammation induced by chronic antigen exposure prevented in TRX transgenic mice that showed the constitutive overproduction of TRX [12].…”

“…In low/moderate concentration of ROS are essential for maintaining normal physiological functions, but excess productions and/or decreased levels in antioxidant(s) lead to oxidative stresses [7,18,19]. TRX is well known to be one of the most important regulators of reduction/oxidation (redox) balance and to inhibit intracellular ROS generation [11][12][13]20], which causes tissue injury at the inflamed site during AR [21,22]. It is reported that TRX suppressed the CC chemokine-induced chemotaxis of eosinophils through inhibition of both activation of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase pathways [22], which play an important role in eosinophil chemotaxis [23].…”

“…TRX is also reported to exert immunomodulatory effects. Treatment of asthmatic model mouse with TRX could suppress the development of airway hyper responsiveness induced by aerosolized acetylcholine [11,12]. It is also reported that administration of exogenous TRX prevents airway remodeling with intense infiltration of both eosinophils and macrophages through the suppression of Th2 cytokine (e.g.…”

“…It is also reported that administration of exogenous TRX prevents airway remodeling with intense infiltration of both eosinophils and macrophages through the suppression of Th2 cytokine (e.g. IL-4 and IL-5) production induced by inhalation of specific allergen [11,12]. Furthermore, TRX is reported to inhibit the production of regulated on activation, normal T cell expressed, and secreted (RANTES)-and eotaxin-induced migration of eosinophils, leading to attenuation of eosinophilic inflammatory responses in airways [13].…”