Expressions of peroxisome proliferator-activated receptors (PPARs) are directly influenced by permeability barrier abrogation and inflammatory cytokines and depressed PPAR modulates expressions of chemokines and epidermal differentiation-related molecules in keratinocytes

Previous studies have demonstrated that the activation of peroxisome proliferator-activated receptors (PPARs) not only has positive effects on permeability barrier homoeostasis but also has anti-inflammatory effects by an as yet unknown mechanism. Reduced expression of PPAR alpha in lesion of human atopic dermatitis (AD) and in epidermis of murine AD-like dermatitis has been demonstrated. This study revealed that expression of PPAR alpha alone among PPARs (alpha, beta/delta and gamma) was suppressed by both permeability barrier abrogation and additional existence of Th2 cytokine in cultured normal human keratinocytes. In addition, expressions of transglutaminase 1 and loricrin and those of thymus and activation-related chemokine and regulated on activation normal T-cell expressed in cultured human keratinocytes were reduced and enhanced, respectively, by transfection with siRNA for PPAR alpha. In conclusion, depressed PPAR alpha in keratinocytes might be involved in a relationship between permeability barrier abrogation and allergic inflammation and could be a therapeutic target which accounts for both the aspects in AD.