title: Semaphorin 7A on keratinocytes induces interleukin-8 production by monocytes.
abstract: BACKGROUND
  Semaphorin 7A (Sema7A) expressed on activated T cells stimulates cytokine production in monocytes through its receptor, α1β1 integrin.
  
  
  OBJECTIVE
  To study the significance of Sema7A expressed on keratinocytes in skin inflammation where interaction between keratinocytes and β1-integrin expressing inflammatory cells, such as monocytes, takes place.
  
  
  METHODS
  The regulation of Sema7A expression on keratinocytes by various cytokines was studied by flow cytometry and immunoblot. β1-integrin expressing human monocyte cell line, THP-1 cells, were co-cultured with paraformaldehyde-fixed normal human epidermal keratinocytes (NHK) and IL-8 production by THP-1 cells was studied. The significance of β1-integrin or Sema7A within this cell interaction was examined by the experiments using β1-integrin blocking antibody or Sema7A siRNA.
  
  
  RESULTS
  IFN-γ and TNF-α slightly increased Sema7A expression, while IL-4 decreased it. Among cytokines tested, TGF-β1 most strikingly increased the Sema7A expression on NHK. When NHK was stimulated by TGF-β1, paraformaldehyde-fixed, and co-cultured with THP-1 cells, IL-8 production by THP-1 cells was increased compared to THP-1 cells only. When THP-1 cells were pretreated with β1-integrin blocking antibody, this increase in IL-8 production by THP-1 cells was inhibited. Likewise, when NHK were pretreated with Sema7A siRNA before fixation and co-cultured with THP-1 cells, increase in IL-8 production by THP-1 cells was inhibited.
  
  
  CONCLUSIONS
  Our results suggest that Sema7A on keratinocytes and β1-integrin on monocytes contribute to monocyte activation by keratinocytes within skin inflammation, such as psoriasis or wound.
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kamata
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Tada
authors.forename: Hideya
authors.initials: H
authors.lastname: Uratsuji
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Kawashima
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Asano
authors.forename: Makoto
authors.initials: M
authors.lastname: Sugaya
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kadono
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Tamaki
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sato
mesh_terms: D015703:Antigens, CD / Q000502:physiology*; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005434:Flow Cytometry / Q000379:methods; D058851:GPI-Linked Proteins / Q000502:physiology; D006801:Humans; D007249:Inflammation; D019012:Integrin beta1 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D011565:Psoriasis / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D039961:Semaphorins / Q000502:physiology*; D014945:Wound Healing
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D017931:DNA Primers; D058851:GPI-Linked Proteins; D019012:Integrin beta1; D016209:Interleukin-8; D034741:RNA, Small Interfering; C118753:SEMA7A protein, human; D039961:Semaphorins