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.
Conclusion: 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.
Keywords: Cell differentiation; IKK alpha; Inflammation; Interleukin-17; Interleukin-22; Keratinocytes.