Increased 1-Deoxysphingolipids and Skin BarrierDysfunction in the Skin of X-ray or Ultraviolet BIrradiation and Atopic Dermatitis Lesion Could BePrevented by Moisturizer with Physiological LipidMixture

ABSTRACT

Background@#Skin diseases characterized by epithelial barrierdysfunction show altered sphingolipid metabolism,which results in changes in the stratum corneum intercellularlipid components and structure. Under pathological conditions,1-deoxysphingolipids form as atypical sphingolipidsfrom de novo sphingolipid biosynthesis. @*Objective@#Thisstudy investigated the potential role of 1-deoxysphingolipidsin skin barrier dysfunction secondary to X-ray and ultravioletB (UVB) irradiation in vitro and in vivo. It was also evaluatedchanges in the expression of 1-deoxysphingolipids in lesionalhuman skin of atopic dermatitis. @*Methods@#In thisstudy, the changes in these 1-deoxysphingolipids levels ofskin and serum samples were investigated in skin barrier dysfunctionassociated with X-ray and UVB irradiation in vitroand in vivo. @*Results@#Increased 1-deoxysphingolipids were observed in cultured normal human epidermal keratinocytesafter X-ray irradiation. X-ray or UVB irradiation increased theproduction of 1-deoxysphingosine in a reconstituted 3-dimensional(3D) skin model. Interestingly, treatment with aphysiological lipid mixture (multi-lamellar emulsion containedpseudoceramide), which can strengthen the epidermalpermeability barrier function, resulted in decreased1-deoxysphingosine formation in a reconstituted 3D skinmodel. Further investigation using a hairless mouse modelshowed similar preventive effects of physiological lipid mixtureagainst 1-deoxysphingosine formation after X-ray irradiation.An increased level of 1-dexoysphingosine in the stratumcorneum was also observed in lesional skin of atopic dermatitis. @*Conclusion@#1-deoxysphingosine might be a novelbiomarker of skin barrier dysfunction and a physiological lipidmixture treatment could prevent 1-deoxysphingosine productionand consequent skin barrier dysfunction.