Nanae Nagata†, Yuta Hamasaki†, Shinichiro Inagaki†, Tatsuro Nakamura†, Daiki Horikami, Kiwako Yamamoto-Hanada, Yusuke Inuzuka, Tatsuo Shimosawa, Koji Kobayashi, Masami Narita, Yukihiro Ohya*, and Takahisa Murata*


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 metabolite (13,14-dihydro-15-keto-tetranor-PGF), a PGE2 metabolite (13,14-dihydro-15-keto-tetranor-PGE2), and a PGD2 metabolite (13,14-dihydro-15-keto PGJ2). mRNA and protein expression of PGF, PGE2, and PGD2 synthase was upregulated in DNFB-treated skin. The tape-stripping model also caused dermatitis but without Th2 inflammation; urine PGF and PGD2 metabolite levels remained unaffected. Finally, we confirmed that the urinary levels of the aforementioned PG metabolites, as well as PGI2 metabolite, 6,15-diketo-13,14-dihydro-PGF 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.

Paper Information

: The FASEB Journal