title: IL-22/STAT3-Induced Increases in SLURP1 Expression within Psoriatic Lesions Exerts Antimicrobial Effects against Staphylococcus aureus.
abstract: BACKGROUND
  SLURP1 is the causal gene for Mal de Meleda (MDM), an autosomal recessive skin disorder characterized by diffuse palmoplantar keratoderma and transgressive keratosis. Moreover, although SLURP1 likely serves as an important proliferation/differentiation factor in keratinocytes, the possible relation between SLURP1 and other skin diseases, such as psoriasis and atopic dermatitis, has not been studied, and the pathophysiological control of SLURP1 expression in keratinocytes is largely unknown.
  
  
  OBJECTIVE
  Our aim was to examine the involvement of SLURP1 in the pathophysiology of psoriasis using an imiquimod (IMQ)-induced psoriasis model mice and normal human epidermal keratinocytes (NHEKs).
  
  
  RESULTS
  SLURP1 expression was up-regulated in the skin of IMQ-induced psoriasis model mice. In NHEKs stimulated with the inflammatory cytokines IL-17, IL-22 and TNF-α, which are reportedly expressed in psoriatic lesions, SLURP1 mRNA expression was significantly up-regulated by IL-22 but not the other two cytokines. The stimulatory effect of IL-22 was completely suppressed in NHEKs treated with a STAT3 inhibitor or transfected with siRNA targeting STAT3. Because IL-22 induces production of antimicrobial proteins in epithelial cells, the antibacterial activity of SLURP1 was assessed against Staphylococcus aureus (S. aureus), which is known to be associated with disease severity in psoriasis. SLURP1 significantly suppressed the growth of S. aureus.
  
  
  CONCLUSIONS
  These results indicate SLURP1 participates in pathophysiology of psoriasis by regulating keratinocyte proliferation and differentiation, and by suppressing the growth of S. aureus.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Moriwaki
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Takada
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nagasaki
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Natsuki
authors.initials: N
authors.lastname: Kubo
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Ishii
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Kose
authors.affiliation: Molecular Diagnostics Project, Kanagawa Cancer Center Research Institute, Yokohama, Kanagawa, Japan.
authors.forename: Taihei
authors.initials: T
authors.lastname: Kageyama
authors.affiliation: Molecular Diagnostics Project, Kanagawa Cancer Center Research Institute, Yokohama, Kanagawa, Japan.
authors.forename: Shoutaro
authors.initials: S
authors.lastname: Tsuji
authors.affiliation: Department of Molecular Pharmacology, Kitasato University School of Pharmacy, Minato-ku, Tokyo, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kawashima
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Misawa
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D000077271:Imiquimod; D007378:Interleukins / Q000494:pharmacology*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011565:Psoriasis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000382:microbiology*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D013211:Staphylococcus aureus / Q000254:growth & development*; D015854:Up-Regulation / Q000187:drug effects*; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics* / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D000634:Aminoquinolines; D000950:Antigens, Ly; D000077271:Imiquimod; D007378:Interleukins; D050796:STAT3 Transcription Factor; D014568:Urokinase-Type Plasminogen Activator; D000097043:Interleukin-22; C545249:SLURP-1 protein, mouse; C048963:SLURP1 protein, human