title: Decreased Expression of Caveolin-1 Contributes to the Pathogenesis of Psoriasiform Dermatitis in Mice.
abstract: Psoriasis is a chronic inflammatory skin disease characterized by excessive proliferation and abnormal keratinocyte development, in which T helper type 17 cells and signal transducer and activator of transcription 3 (STAT3) activation have pivotal roles. Moreover, caveolin-1 (CAV-1) has been implicated in the regulation of signal transduction, and aberrant CAV-1 expression is involved in a variety of diseases. However, whether CAV-1 is involved in psoriasis is unknown. Here we examined CAV-1 expression in the psoriatic epidermis and investigated its role in the pathogenesis of psoriasis. CAV-1 was markedly reduced in lesional epidermis of psoriasis patients. CAV1 silencing in keratinocytes in vitro revealed significant activation of STAT3, leading to increased expression of keratin 16 and several cytokine/chemokines, such as IL-6, C-X-C chemokine ligand 8 (CXCL8), CXCL9, and C-C chemokine ligand 20. In addition, psoriasis-related cytokines, including tumor necrosis factor-α (TNF-α), decreased CAV-1 expression in keratinocytes. Finally, administration of CAV-1 scaffolding domain peptide in a murine model of psoriasis-like skin inflammation induced by imiquimod improved the skin phenotype and reduced epidermal thickness and infiltrating cell counts. Furthermore, expression of TNF-α, IL-17A, and IL-23 was significantly suppressed by this treatment. Collectively, our study indicated that CAV-1 participates in the pathogenesis of psoriasis by regulating the STAT3 pathway and cytokine networks.
authors.affiliation: Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. Electronic address: yui1783@yokohama-cu.ac.jp.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Yamaguchi
authors.affiliation: Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Komitsu
authors.affiliation: Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Aihara
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001707:Biopsy, Needle; D015153:Blotting, Western; D051242:Caveolin 1 / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D000077271:Imiquimod; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction / Q000379:methods; D011565:Psoriasis / Q000235:genetics* / Q000473:pathology*; D011897:Random Allocation; D050796:STAT3 Transcription Factor / Q000235:genetics*; D012494:Sampling Studies; D015398:Signal Transduction
chemical_list: D000634:Aminoquinolines; D015415:Biomarkers; D051242:Caveolin 1; D016207:Cytokines; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D000077271:Imiquimod