Recent developments in the role of reactive oxygen species in allergic asthma

Abstract

Allergic asthma has a global prevalence, morbidity, and mortality. Many environmental factors, such as pollutants and allergens, are highly relevant to allergic asthma. The most important pathological symptom of allergic asthma is airway inflammation. Accordingly, the unique role of reactive oxygen species (ROS) had been identified as a main reason for this respiratory inflammation. Many studies have shown that inhalation of different allergens can promote ROS generation. Recent studies have demonstrated that several pro-inflammatory mediators are responsible for the development of allergic asthma. Among these mediators, endogenous or exogenous ROS are responsible for the airway inflammation of allergic asthma. Furthermore, several inflammatory cells induce ROS and allergic asthma development. Airway inflammation, airway hyper-responsiveness, tissue injury, and remodeling can be induced by excessive ROS production in animal models. Based on investigations of allergic asthma and ROS formation mechanisms, we have identified several novel anti-inflammatory therapeutic treatments. This review describes the recent data linking ROS to the pathogenesis of allergic asthma.

Keywords: Allergic asthma; antioxidants; reactive oxygen species (ROS).

Figure 1

This schematic diagram shows the proposed redox activation mechanism of asthma. Antigen-presenting DCs recognize and present allergens to T cells in the lymph nodes, leading to CD4⁺ cell activation and IL-4, IL-5 and IL-13 production. IL-4 activation of B cells results in the production of allergic specific IgE, which binds with its receptor, FcεRI, located on mast cells to regulate ROS. IL-5 can generate and activate eosinophils to mediate ROS generation. IL-13 was found to be necessary for AHR and goblet cell metaplasia. Meanwhile, TNF-α, IL-1, CuONPs, PAR-2 and NLRP3 were reported to induce ROS and mediate allergic asthma. However, resiquimod, morin, Oxi-CaMKII inhibitor, LTC₄ inhibitor, galangin, astragalin, glutathione, SOD, glutathione peroxidases, and vitamins C and E inhibit ROS generation. DC, dendritic cell; IL-4, interleukin-4; IgE, immunoglobulin E; ROS, reactive oxygen species; AHR, airway hyper-reactivity; TNF-α, tumor necrosis factor-α; CuONPs, copper oxide nanoparticles; PAR-2, proteinase-activated receptor 2; Oxi-CaMKII, oxidative-CaMKII; LTC₄, leukotriene C4; SOD, superoxide dismutase.