Abstract
Excessive exposure to UV, especially UVB, is the most important risk factor for skin cancer and premature skin aging. The identification of the specialized pro-resolving lipid mediators (SPMs) challenged the preexisting paradigm of how inflammation ends. Rather than a passive process, the resolution of inflammation relies on the active production of SPMs, such as Lipoxins (Lx), Maresins, protectins, and Resolvins. LXA4 is an SPM that exerts its action through ALX/FPR2 receptor. Stable ALX/FPR2 agonists are required because SPMs can be quickly metabolized within tissues near the site of formation. BML-111 is a commercially available synthetic ALX/FPR2 receptor agonist with analgesic, antioxidant, and anti-inflammatory properties. Based on that, we aimed to determine the effect of BML-111 in a model of UVB-induced skin inflammation in hairless mice. We demonstrated that BML-111 ameliorates the signs of UVB-induced skin inflammation by reducing neutrophil recruitment and mast cell activation. Reduction of these cells by BML-111 led to lower number of sunburn cells formation, decrease in epidermal thickness, collagen degradation, cytokine production (TNF-α, IL-1β, IL-6, TGF, and IL-10), and oxidative stress (observed by an increase in total antioxidant capacity and Nrf2 signaling pathway), indicating that BML-111 might be a promising drug to treat skin disorders.
Highlights
UV presents benefits to human health by mediating natural synthesis of vitamin D and endorphins in the skin
Treatment with BML-111 at 0.1 mg/kg reduced UVB-induced neutrophil recruitment, this dose was chosen for the following experiments (Figure 1A)
P < 0.05 compared to BML-111 group. In this we demonstrate thatthat the LXA4 receptor agonist
Summary
UV presents benefits to human health by mediating natural synthesis of vitamin D and endorphins in the skin. Recreational UV exposure as a result of cosmetic purposes (tanning beds) has risen steeply over the last several years based on the misconception that a tanned look is associated with better health [7]. This activity has had a significant impact on the increasing incidence of skin cancers in the past years [7,8] and underscores the need for novel therapies to treat skin disorders alongside efforts to educate the public and government about the dangers of UV radiation
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