Methods: FBP, including pyrrolidone carboxylic acid (PCA) and urocanic acid (UCA) were quantitated in stratum corneum (SC) samples collected from volar forearm regions (6 consecutive tapes) employing UPLC-MS/MS from 10 CSU, 10 atopic dermatitis (AD) and 10 normal subjects. In vitro effects of cis- and trans-UCA on human mast cell degranulation were assessed by beta-hexosaminidase release assay using LAD2 cells.
Results: With normalization by protein content, total amount of FBP and PCA content was significantly decreased in lesional (21.56±20.2 and 16.70±15.4 ng/mg protein, respectively, P<0.01) AD skins as compared to NC (63.86±21.6 and 49.14±16.3). However, those were not significantly different in CSU lesions (44.54±31.2 and 34.48±23.6) compared with NC. Trans-UCA, the primary isomer of the UCA in NC, was significantly decreased in CSU and AD. The proportion of cis-UCA was significantly higher in CSU skin (0.44±0.24, P<0.01) compared with AD (0.14±0.20) and NC (0.10±0.12). Both TEWL and pH were significantly increased in AD lesions compared with CSU lesions. Cis-UCA dose-dependently enhanced the IgE- and calcium-mediated degranulation of LAD2 cells (P<0.001), which was not observed with trans-UCA.
Conclusions: FBP deficiency in AD was confirmed in the association with a significant increase in TEWL and pH in AD. Increased ratio of cis-to-trans-UCA, and decreased epidermal pH in CU can be associated with CU pathogenesis. Cis-UCA could contribute to the pathogenesis of CU by enhancing mast cell degranulation.