Abstract
Abstract The pathogenesis of psoriasis may involve the IL-23 and Th17-mediated immune responses. Th17 cells secret IL-17 and IL-22 which mediates dermal inflammation and acanthosis. As 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. We employed HaCaT cells maintained culture medium at a low calcium concentration (0.06 mM) and induced differentiation by switching high concentration (2.8 mM) media with IL-17 or IL-22, then compared IKKα expression and the cell cycle. We employed reconstituted human epidermal skin (Neoderm) and mice ears for the in vivo studies. 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. 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 inflammation occurring via the induction of IKKα from keratinocytes or skin layers.
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