Pretreatment with acetylsalicylic acid alleviates UVB irradiation-induced skin pathology in hairless mice and BOC-2 (an ALX/FPR2 receptor antagonist) reduces its activity

This work aims to investigate if the biological activity of acetylsalicylic acid (ASA) against UVB irradiation-induced skin inflammatory and oxidative injury in hairless mice would be amenable by treatment with BOC-2, an antagonist of the formyl peptide receptor 2 receptor (ALX/FPR2). Mice were treated with BOC-2 and after 30 minutes, they received ASA or Aspirin-Triggered 15-epi-lipoxin A₄ (AT-LXA_4, an agonist of ALX/FPR2), and after 1 hour, they were exposed to UVB irradiation (dose of 4.14 J/cm²). UVB stimulation induced neutrophil and mast cell recruitment, edema, matrix metalloproteinase-9 (MMP-9) activity, collagen degradation, sunburn cell formation, and cytokine production (TNF-α, IL-1β and IL-6). All these parameters were inhibited by ASA or AT-LXA₄. In addition, ASA and AT-LXA₄ enhanced anti-inflammatory cytokines (IL-10 and TGF-β), and attenuated UVB-induced oxidative damage returning the oxidative status to baseline levels in parameters such as ferric reducing ability, free radical scavenging, reduced glutathione levels, catalase activity, superoxide anion production, Nrf2, Nqo1, and gp91^phox mRNA expression. These therapeutic effects of ASA and AT-LXA₄ were reversed by BOC-2. Our results demonstrate that ALX/FPR2 receptor plays an important role in ASA activity against UVB-induced skin pathologies.