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

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.