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Subclinical cutaneous inflammation remained after permeability barrier disruption enhances UV sensitivity by altering ER stress responses and topical pseudoceramide prevents them

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Abstract

Stratum corneum forms the UV barrier. The effect of ultraviolet B (UVB) on normal skin was extensively studied; however, its effect on barrier perturbed skin remains undefined. Both barrier perturbation and UVB irradiation induce endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in keratinocytes. Mild ER stress activates homeostatic UPR, while severe ER stress leads to abnormal UPR, promoting apoptosis and inflammation. Here, we investigated UV sensitivity and UVB-induced UPR in barrier-disrupted human skin and the effects of pseudoceramide-dominant emollient on UVB-induced skin responses. Tape-stripped skin of healthy volunteers showed enhanced susceptibility to erythema and augmented proinflammatory cytokines induction following suberythemal UVB irradiation. Suberythemal UVB activated XBP1 in normal skin, while increased CHOP transcription in barrier perturbed skin. After tape stripping, pseudoceramide-dominant emollient was applied for 3 days, and then, the areas were irradiated with suberythemal UVB. Pretreatment with topical pseudoceramide protected against UVB-induced upregulation of IL-1β, IL-6, and TNF-α transcription and reduced susceptibility to erythema following UVB. Topical pseudoceramide also suppressed suberythemal UVB-induced CHOP transcription in barrier-disrupted skin. Taken together, these data indicate that permeability barrier disruption increases UV sensitivity in human skin, partly via switch the UVB-induced UPR, from homeostatic signals to pro-apoptotic and proinflammatory signals. In addition, we conclude that pseudoceramide-dominant emollient suppresses excessive ER stress induction and CHOP activation following UVB in barrier damaged skin, providing evidence that pseudoceramide-dominant emollients can be promising strategies for photoprotection of the barrier damaged skin.

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Abbreviations

UVB:

Ultraviolet B

ER:

Endoplasmic reticulum

UPR:

Unfolded protein response

SC:

Stratum corneum

PERK:

PKR-like ER kinase

CHOP:

C/EBP homologous protein

PPAR:

Peroxisome proliferator-activated receptor

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Acknowledgements

We thank other members of the Kao Corporation for cooperation in the study and DermaPro members for assistance in the clinical trial.

Author information

Authors and Affiliations

  1. Department of Dermatology, Gangnam Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, 211 Eonjuro, Gangnam-gu, Seoul, 06273, Korea

    Sang Eun Lee & Seung Hun Lee

  2. Kao Corporation, Tokyo, Japan

    Yutaka Takagi & Takahiro Nishizaka

  3. Skin Research Center, DERMAPRO LTD., Seoul, Korea

    Ji Hwoon Baek & Han Jo Kim

Authors
  1. Sang Eun Lee
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  2. Yutaka Takagi
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  3. Takahiro Nishizaka
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  4. Ji Hwoon Baek
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  5. Han Jo Kim
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  6. Seung Hun Lee
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Contributions

Author contributions

SEL performed experiments, analyzed the data, and wrote the manuscript. UT contributed to the design of the study. JHB and HJK conceived the method and performed experiments. SHL guided experiments and assisted in drafting and editing the manuscript.

Corresponding author

Correspondence to Seung Hun Lee.

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Conflict of interest

No conflict of interest by disclosing any financial arrangements in this paper. This study was supported financially by Kao Corporation, Tokyo Japan.

Ethical approval

This study was approved by the Institutional Review Board of the DERMAPRO/Skin Research Center, Seoul, Korea (DERMAPRO Ltd. IRB, IORG0005011-DICN13001).

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Lee, S.E., Takagi, Y., Nishizaka, T. et al. Subclinical cutaneous inflammation remained after permeability barrier disruption enhances UV sensitivity by altering ER stress responses and topical pseudoceramide prevents them. Arch Dermatol Res 309, 541–550 (2017). https://doi.org/10.1007/s00403-017-1753-0

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  • DOI: https://doi.org/10.1007/s00403-017-1753-0

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