Expressions of peroxisome proliferator-activated receptors (PPARs) are directly influenced by permeability barrier abrogation and inflammatory cytokines and depressed PPARα 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 PPARα in lesion of human atopic dermatitis (AD) and in epidermis of murine AD-like dermatitis has been demonstrated. This study revealed that expression of PPARα alone among PPARs (α, β/δ and γ) 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 PPARα. In conclusion, depressed PPARα 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.
Department of Dermatology, Faculty of Medicine, Oita University, Yufu-shi, Japan.
Yasuko
Y
Adachi
Yutaka
Y
Hatano
Takashi
T
Sakai
Sakuhei
S
Fujiwara
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000378:metabolism / Q000473:pathology; D055785:Gene Knockdown Techniques; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D047493:PPAR alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010539:Permeability; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics
D018925:Chemokines; D016207:Cytokines; C508598:IL4 protein, human; D018836:Inflammation Mediators; D047493:PPAR alpha; D047492:Peroxisome Proliferator-Activated Receptors; D034741:RNA, Small Interfering; D015847:Interleukin-4
IL-4; PPARα; barrier abrogation; chemokines