Urinary lipid profile of atopic dermatitis in murine model and human patients

Abstract Atopic dermatitis (AD) is the most common inflammatory skin disease in children. The serum level of thymus and activation‐regulated chemokine (TARC) is a useful AD index to reflect disease severity; however, it requires blood collection from young children. In comparison, urine samples are easier to collect in a pediatric clinical setting. Here, we analyzed the lipids excreted in urine to identify a diagnostic biomarker for AD. We generated a murine dermatitis model by repeated topical application of 2,4‐dinitrofluorobenzene (DNFB) or tape‐stripping the dorsal skin. Lipid metabolites excreted in the urine were comprehensively analyzed using liquid chromatography‐tandem mass spectrometry. To corroborate our findings, we also analyzed urine samples from patients with AD. DNFB application induced AD‐like skin lesions, including epidermal thickening, infiltration of eosinophils and T cells, and an increase in Th2 cytokine levels. Assessment of lipids excreted in urine showed a dominance of prostaglandins (PGs), namely, a PGF 2α metabolite (13,14‐dihydro‐15‐keto‐tetranor‐PGF 1α ), a PGE 2 metabolite (13,14‐dihydro‐15‐keto‐tetranor‐PGE 2 ), and a PGD 2 metabolite (13,14‐dihydro‐15‐keto PGJ 2 ). mRNA and protein expression of PGF 2α , PGE 2 , and PGD 2 synthase was upregulated in DNFB‐treated skin. The tape‐stripping model also caused dermatitis but without Th2 inflammation; urine PGF 2α and PGD 2 metabolite levels remained unaffected. Finally, we confirmed that the urinary levels of the aforementioned PG metabolites, as well as PGI 2 metabolite, 6,15‐diketo‐13,14‐dihydro‐PGF 1α and arachidonic acid metabolite, 17‐hydroxyeicosatetraenoic acid (17‐HETE) increased in patients with AD. Our data highlights the unique urinary lipid profile in patients with AD, which may provide insight into novel urinary biomarkers for AD diagnosis.