Oxidative Stress and Phototherapy in Atopic Dermatitis: Mechanisms, Role, and Future Perspectives

Abstract

Atopic dermatitis is a chronic inflammatory skin disease in which the overproduction of reactive oxygen species plays a pivotal role in the pathogenesis and persistence of inflammatory lesions. Phototherapy represents one of the most used therapeutic options, with benefits in the clinical picture. Studies have demonstrated the immunomodulatory effect of phototherapy and its role in reducing molecule hallmarks of oxidative stress. In this review, we report the data present in literature dealing with the main signaling molecular pathways involved in oxidative stress after phototherapy to target atopic dermatitis-affected cells. Since oxidative stress plays a pivotal role in the pathogenesis of atopic dermatitis and its flare-up, new research lines could be opened to study new drugs that act on this mechanism, perhaps in concert with phototherapy.

Keywords: NRF2; PON1; UVA; UVB; atopic dermatitis; oxidative stress; phototherapy; reactive oxygen species; skin disease; ultraviolet.

Figure 1

Oxidative stress causes direct damage to the cell membrane and DNA which leads to skin barrier defect. Furthermore, the activation of the NF-κB pathway leads to the release of IL-6, IL-8, IL-9, and IL-33. The defect of the skin barrier causes inflammation of the dermis and release of histamine and itching, leading in turn to an increased release of IL-6, IL-8, IL-9, and IL-33. All these mechanisms determine a further increase in the release of ROS, establishing a vicious circle that is self-maintaining. Created with BioRender.com.

Figure 2

UVR modulation on the expression of cytoprotective genes. The figure shows the diametrically opposite effects of UVA and UVB. UVA-mediated oxidation acts on two different levels by promoting the intracytoplasmic accumulation of free NRF2 which, once oxidized, translocates to the nucleus where, dimerizing with AP-1, it acts as a transcriptional activator of cytoprotective genes. Further upregulation of HMOX-1 is provided by the oxidation of HIF-1. UVB-mediated oxidation indirectly inactivates the transcription of cytoprotective genes through direct DNA damage. The lack of this cytoprotective action in turn results in NLRP3 inflammasome activation and consequent pyroptosis.