title: 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.
authors.affiliation: Faculty of Medicine, Department of Dermatology, Oita University, Yufu-shi, Japan.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Faculty of Medicine, Department of Dermatology, Oita University, Yufu-shi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakai
authors.affiliation: Faculty of Medicine, Department of Dermatology, Oita University, Yufu-shi, Japan.
authors.forename: Sakuhei
authors.initials: S
authors.lastname: Fujiwara
authors.affiliation: Faculty of Medicine, Department of Dermatology, Oita University, Yufu-shi, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hatano
mesh_terms: D002478:Cells, Cultured; D054414:Chemokine CCL17 / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D047493:PPAR alpha / Q000819:agonists*; D011743:Pyrimidines / Q000494:pharmacology*
chemical_list: C106230:CCL17 protein, human; C483024:CCL5 protein, human; D054414:Chemokine CCL17; D018946:Chemokine CCL5; D047493:PPAR alpha; D011743:Pyrimidines; C006253:pirinixic acid