Journal
JOURNAL OF DERMATOLOGICAL SCIENCE
Volume 92, Issue 1, Pages 54-61Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.jdermsci.2018.07.008
Keywords
Permeability barrier; STAT6; Steady states
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Funding
- Trust Accounts in Oita University
- Japan Society for the Promotion of Science [26461662, 17K10214]
- Grants-in-Aid for Scientific Research [26461662, 17K10214] Funding Source: KAKEN
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Background: Th2 cytokines exhibit a variety of inhibitory effects on permeability barrier function via signal transducer and activator of transcription 6 (STAT6). However, the role of STAT6 signaling on the construction and/or homeostasis of permeability barrier function in the physiological state has not been fully assessed. Objective: We compared permeability barrier function between Stat6-deficient and wild-type C57BL/6 mice at steady state. Methods and results: Measurement of transepidermal water loss and quantitative penetration assay revealed that permeability barrier function was superior in Stat6-deficient mice. Accordingly, expressions of loricrin, acidic sphingomyelinase (aSMase) and beta-glucocerebrosidase (beta-GlcCer'ase) in epidermis and ceramide levels in stratum corneum were elevated in STAT6-deficient mice. On the other hands, up-regulations of loricrin, aSMase and beta-GlcCer'ase were not observed in 3-dimensionally cultured human keratinocytes transfected with siRNA for STAT6. Meanwhile, number of mast cells in the dermis was decreased in Stat6-deficient mice. Conclusions: These results suggest that STAT6 signaling negatively affects permeability barrier function in vivo, even in the physiological state. However, the superior permeability barrier function in Stat6-deficient mice may be a secondary effect exerted via cells other than keratinocytes, such as mast cells, since mast cells are known to influence permeability barrier function in vivo. Blockade of STAT6 signaling might be a strategy to augment the permeability barrier function. (C) 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.
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