Melatonin prevents allergic airway inflammation in epicutaneously sensitized mice

Abstract

Purpose: The pathological process of atopic dermatitis (AD) progressing into other types of allergic diseases such as asthma and allergic rhinitis during the first several years of life is often referred to as the atopic march. Although the phenomenon of atopic march has been recognized for decades, how asthma stems from AD is still not fully understood, confounding a universal strategy to effectively protect people from the atopic march. Methods: We established experimental atopic march mice by first inducing allergic dermatitis with 0.5% fluorescein isothiocyante applied to the skin, followed by an OVA airway challenge. In addition, by examining serum immunoglobulin concentrations, airway cytokines, the levels of oxidative stress markers, histopathological changes in lung tissue and airway hyperresponsiveness, we were able to validate the successful establishment of the model. Furthermore, by detecting the attenuating effects of melatonin (MT) and the levels of oxidative stress in the atopic march mice, we explored the potential molecular mechanisms involved in the development of atopic march. Results: By successfully establishing an experimental atopic march mouse model, we were able to demonstrate that overproduction of oxidative stress in the lung significantly upregulated the activation of NF-κB signaling pathways causing TSLP release, which further promotes the development of atopic march. Conclusions: To mitigate the development of the atopic march, antioxidants such as MT may be imperative to inhibit NF-κB activation in the lung, especially after the onset of AD.

Melatonin in Dermatologic Allergic Diseases and Other Skin Conditions: Current Trends and Reports

“…Thus, atopic dermatitis in childhood often progresses to other types of allergic diseases such as asthma and allergic rhinitis. This process is called the atopic march (a combination of atopic dermatitis, allergic rhinitis and allergic asthma), although the specific explanation of how asthma arises from atopic dermatitis is still not fully understood [ 63 ]. Oxidative stress is one of the key pathogenetic mechanisms in the development of allergic asthma.…”

“…Oxidative stress is one of the key pathogenetic mechanisms in the development of allergic asthma. According to previous studies on allergic asthma, there is a potential link between increased oxidative damage and the occurrence/exacerbation of allergic asthma, with thymic stromal lymphopoeitin (TSLP) playing the key role in the atopic march, by stimulating sensitization to allergens in the skin with a damaged barrier [ 63 ]. According to results from research on an experimental atopic march mouse model, in lung cells, oxidative stress significantly activates NF-κB signaling pathways, which cause TSLP release, again illustrating melatonin’s antioxidant properties [ 62 ].…”

“…According to results from research on an experimental atopic march mouse model, in lung cells, oxidative stress significantly activates NF-κB signaling pathways, which cause TSLP release, again illustrating melatonin’s antioxidant properties [ 62 ]. According to literature data, melatonin treatment, in addition to reducing the production of free oxygen radicals, also reduces the level of lipid peroxidation [ 63 ]. From a therapeutic point of view, in the lungs, antioxidants such as melatonin can inhibit the activation of NF-κB, especially after the onset of atopic dermatitis [ 63 ].…”

“…According to literature data, melatonin treatment, in addition to reducing the production of free oxygen radicals, also reduces the level of lipid peroxidation [ 63 ]. From a therapeutic point of view, in the lungs, antioxidants such as melatonin can inhibit the activation of NF-κB, especially after the onset of atopic dermatitis [ 63 ]. In the pathogenesis of allergic diseases, Th2 and Th1 cells are very important pathogenetic factors.…”

“…According to the results of an experimental study on mice with the atopic march, the excessive development of oxidative stress in the lungs significantly activated the signaling pathway (NF-κB), which caused the further release of pro-inflammatory cytokines and the development of an inflammatory reaction in atopic diseases [ 63 ]. The use of antioxidants, such as melatonin in atopic disorders, can also be directed to reduce the activation of NF-κB in the lungs, especially after the onset of atopic dermatitis [ 63 ]. So, the role of oxidative stress is very important for allergic disorders.…”