title: Interleukin-17 and Interleukin-22 Induced Proinflammatory Cytokine Production in Keratinocytes via Inhibitor of Nuclear Factor κB Kinase-α Expression.
abstract: BACKGROUND
  The pathogenesis of psoriasis may involve the interleukin (IL)-23 and Th17-mediated immune responses. Th17 cells secret IL-17 and IL-22, which mediates dermal inflammation and acanthosis.
  
  
  OBJECTIVE
  As inhibitor of nuclear factor κB kinase-α (IKKα) has been previously identified as a primary regulator of keratinocyte differentiation and proliferation, we proposed that IL-17 and IL-22 might affect keratinocyte differentiation by changing the expression of IKKα.
  
  
  METHODS
  We employed HaCaT cells maintained culture medium at a low calcium concentration (0.06 mM) and induced differentiation by switching to the high concentration (2.8 mM) media with IL-17 or IL-22, then compared the IKKα expression and the cell cycle. We employed reconstituted human epidermal skin (Neoderm) and mice ears for the in vivo studies.
  
  
  RESULTS
  Elevated calcium concentration induced IKKα expression and terminal differentiation with cell cycle arrest in HaCaT cell cultures. Moreover, IL-17 and IL-22 treatment also induced IKKα in HaCaT cells and reconstituted human epidermis. IKKα induction was also noted, following the injection of IL-17 and IL-22 into mice ears.
  
  
  CONCLUSIONS
  Although the induction of IKKα was accompanied by keratinocyte differentiation, IL-17 and IL-22 did not affect calcium-mediated differentiation or the cell cycle. Rather, IL-17 and IL-22 appear to contribute to the inflammation occurring via the induction of IKKα from keratinocytes or skin layers.
authors.affiliation: Department of Microbiology, School of Medicine, Ewha Womans University, Seoul, Korea.
authors.forename: Kyung-Ah
authors.initials: KA
authors.lastname: Cho
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: So-Youn
authors.initials: SY
authors.lastname: Woo
authors.forename: Hyun Jeong
authors.initials: HJ
authors.lastname: Park
authors.forename: Kyung Ho
authors.initials: KH
authors.lastname: Lee
authors.forename: Chi-Un
authors.initials: CU
authors.lastname: Pae