Interleukin-17 and Interleukin-22 Induced Proinflammatory Cytokine Production in Keratinocytes via Inhibitor of Nuclear Factor κ B Kinase-α Expression

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 kappa B kinase-alpha (IKK alpha) 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 IKK alpha. 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 IKK alpha 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 IKK alpha expression and terminal differentiation with cell cycle arrest in HaCaT cell cultures. Moreover, IL-17 and IL-22 treatment also induced IKK alpha in HaCaT cells and reconstituted human epidermis. IKK alpha induction was also noted, following the injection of IL-17 and IL-22 into mice ears. Conclusion: Although the induction of IKK alpha 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 IKK alpha from keratinocytes or skin layers. (Ann Dermatol 24(4) 398 similar to 405, 2012)