Wy14643, an agonist for PPARα, downregulates expression of TARC and RANTES in cultured human keratinocytes

Abstract

Beneficial effects of Wy14643, an agonist for peroxisome proliferator-activated receptor (PPAR)α, on permeability barrier homeostasis-related functions of keratinocytes such as up-regulation of epidermal differentiation-related molecules and lipid synthesis, have been demonstrated. The present study demonstrated that Wy14643 reduced the expression of thymus and activation-related chemokine (TARC) and regulated on activation normal T cell expressed (RANTES) in both single- and 3D-cultured human keratinocytes. The combined data of the present and previous studies support the notion that Wy14643 could be a therapeutic agent that might simultaneously and directly modulate permeability barrier dysfunction and allergic inflammation in the pathogenesis of atopic dermatitis. As for the anti-microbial barrier function, the present study demonstrated that Wy14643 up-regulated expression of the anti-microbial peptide, human β defensin 3, in cultured human keratinocytes only in mRNA levels but not in protein ones, suggesting that Wy14643 might not directly account for the up-regulation of the anti-microbial peptide which has been reported in vivo.