Topical application of PPARα (but not β/δ or γ) suppresses atopic dermatitis in NC/Nga mice

Background: Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors, which regulate not only adipogenesis and proliferation/ differentiation but also the immune response of cells. Because topical application of the activators of some PPAR isoforms improved clinical symptoms in patients with atopic dermatitis (AD), we investigated the role of PPAR activators using a murine AD model in NC/Nga mice; to the best of our knowledge, this has not been previously reported. Methods: Activators of three PPAR isoforms (α, β/δ, γ) were topically applied on inflamed skin in a murine AD model that was developed by repeated topical application of mite antigen in NC/Nga mice. The efficacy of each topical PPAR activator was evaluated immunologically and serologically. Results: Topical application of the PPARα activator, but not of the activators of PPARβ/δ or PPARγ, improved clinical dermatitis, reduced inflammatory cell infiltration in the dermis, and alleviated the elevation of serum IgE levels. In addition, PPARa expression was downregulated in the epidermis in our murine AD model, as is seen in patients with AD. Conclusions: Topical application of PPARα activator could be a potent therapeutic agent for patients with AD and could take the place of topical steroid treatments.