Lipoxin A4 inhibits UV radiation-induced skin inflammation and oxidative stress in mice.

Background: Lipoxin A4 (LXA ₄ ) is a metabolic product of arachidonic acid. Despite potent anti-inflammatory and pro-resolution activities, it remains to be determined if LXA ₄ has effect on ultraviolet (UV) radiation-induced skin inflammation.
Objective: To investigate the effects of systemic administration with LXA ₄ on UV radiation-induced inflammation and oxidative damage in the skin of mice.
Methods: Varied parameters of inflammation and oxidative stress in the skin of mice were evaluated after UV radiation (4.14 J/cm ² ).
Results: Pretreatment with LXA ₄ significantly inhibited UV radiation-induced skin edema and myeloperoxidase activity. LXA ₄ efficacy was enhanced by increasing the time of pre-treatment to up to 72 h. LXA ₄ reduced UV radiation-induced skin edema, neutrophil recruitment (myeloperoxidase activity and LysM-eGFP ⁺ cells), MMP-9 activity, deposition of collagen fibers, epidermal thickness, sunburn cell counts, and production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-33). Depending on the time point, LXA ₄ increased the levels of anti-inflammatory cytokines (TGF-β and IL-10). LXA ₄ significantly attenuated UV radiation-induced oxidative damage returning the oxidative status to baseline levels in parameters such as ferric reducing ability, scavenging of free radicals, GSH levels, catalase activity and superoxide anion production. LXA ₄ also reduced UV radiation-induced gp91 ^phox [nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) subunit] mRNA expression and enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target enzyme nicotinamide adenine dinucleotide (phosphate) quinone oxidoreductase (Nqo1) mRNA expression.
Conclusion: LXA ₄ inhibited UV radiation-induced skin inflammation by diminishing pro-inflammatory cytokine production and oxidative stress as well as inducing anti-inflammatory cytokines and Nrf2.
(Copyright © 2018. Published by Elsevier B.V.)