Activation of keratinocyte protein kinase Cζ in psoriasis plaques

PKCζ (protein kinase C-ζ), a member of protein kinase C family, plays an important role in cell proliferation, differentiation, and apoptosis. It acts as a downstream molecule for TNF-α (tumor necrosis factor) signal transduction and also regulates the expression of CD1d, an HLA-class I-like molecule. The interaction of CD1d with natural killer T (NKT) cells has been shown to be important in their Th1 cytokine production in psoriasis. In this study, we examined PKCζ in psoriasis in order to define its role in the pathogenesis of the disease. We found that T-cell receptor (TCR) Vα24+Vβ11+ NKT cells and CD1d molecules within psoriatic skin were increased. Moreover, there was an associated increase in PKCζ mRNA and protein expression with membrane translocation in psoriasis lesions compared to uninvolved skin. Furthermore, cultured keratinocytes exhibited increased PKCζ activity and membrane translocation upon stimulation by TNF-α, a cytokine known to play an important role in the pathogenesis of psoriasis. These results implied that PKCζ is an important transduction molecule downstream of TNF-α signaling and is associated with increased expression of CD1d that may enhance CD1d-NKT cell interactions in psoriasis lesions. This makes PKCζ a tempting target for possible pharmacological intervention in modifying the downstream effects of TNF-α in psoriasis.