Masato Kakeda1, Michel Arock2, Christoph Schlapbach3, Nikhil Yawalkar4. 1. Department of Dermatology, Inselspital, Bern University Hospital, Bern, Switzerland; Department of Dermatology, Mie University Graduate School of Medicine, Mie, Japan. 2. Laboratoire Central d'Hématologie, Groupe Hospitalier Pitié-Salpêtrière (Paris), and LBPA, CNRS UMR 8113, Ecole Normale Supérieure de Cachan, Cachan, France. 3. Department of Dermatology, Inselspital, Bern University Hospital, Bern, Switzerland. Electronic address: christoph.schlapbach@insel.ch. 4. Department of Dermatology, Inselspital, Bern University Hospital, Bern, Switzerland.
Abstract
BACKGROUND: Psoriasis is a chronic inflammatory skin disease and various stress factors mediate inflammation. Heat shock protein (HSP) 90 plays an important role in cell survival; cytokine signaling, such as interleukin-17 receptor signaling; and immune responses. OBJECTIVE: We sought to elucidate protein expression and distribution of HSP90 in psoriasis. METHODS: HSP90 expression and its cellular source were analyzed on normal-appearing, nonlesional, lesional, and ustekinumab-treated psoriatic skin using immunohistochemistry and double immunofluorescence. RESULTS: HSP90α, the inducible isoform of HSP90, was significantly up-regulated in epidermal keratinocytes and mast cells of lesional skin and down-regulated after ustekinumab therapy. LIMITATIONS: There was a limited sample size. CONCLUSIONS: HSP90 from keratinocytes and mast cells is a key regulator of psoriatic inflammation and HSP90 inhibitors may represent a novel therapeutic approach to the disease.
BACKGROUND:Psoriasis is a chronic inflammatory skin disease and various stress factors mediate inflammation. Heat shock protein (HSP) 90 plays an important role in cell survival; cytokine signaling, such as interleukin-17 receptor signaling; and immune responses. OBJECTIVE: We sought to elucidate protein expression and distribution of HSP90 in psoriasis. METHODS:HSP90 expression and its cellular source were analyzed on normal-appearing, nonlesional, lesional, and ustekinumab-treated psoriatic skin using immunohistochemistry and double immunofluorescence. RESULTS:HSP90α, the inducible isoform of HSP90, was significantly up-regulated in epidermal keratinocytes and mast cells of lesional skin and down-regulated after ustekinumab therapy. LIMITATIONS: There was a limited sample size. CONCLUSIONS:HSP90 from keratinocytes and mast cells is a key regulator of psoriatic inflammation and HSP90 inhibitors may represent a novel therapeutic approach to the disease.