1. ¹Department of Dermatology, University of Maryland School of Medicine, Baltimore, Maryland, USA
2. ²Department of Dermatology, the First Hospital of China Medical University, Shenyang, China
3. ³Comparative Pathology Branch, Comparative Medicine Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland, USA
4. ⁴Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, USA

Correspondence: Anthony A. Gaspari, Department of Dermatology, University of Maryland School of Medicine, 405 W. Redwood St., 6th Floor, Baltimore, Maryland 21201, USA. E-mail: agasp001@umaryland.edu

Received 28 June 2007; Revised 1 February 2008; Accepted 9 February 2008; Published online 3 April 2008.

Abstract

PKC (protein kinase C-), 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- (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 PKC in psoriasis in order to define its role in the pathogenesis of the disease. We found that T-cell receptor (TCR) V24+V11+ NKT cells and CD1d molecules within psoriatic skin were increased. Moreover, there was an associated increase in PKC mRNA and protein expression with membrane translocation in psoriasis lesions compared to uninvolved skin. Furthermore, cultured keratinocytes exhibited increased PKC activity and membrane translocation upon stimulation by TNF-, a cytokine known to play an important role in the pathogenesis of psoriasis. These results implied that PKC is an important transduction molecule downstream of TNF- signaling and is associated with increased expression of CD1d that may enhance CD1d–NKT cell interactions in psoriasis lesions. This makes PKC a tempting target for possible pharmacological intervention in modifying the downstream effects of TNF- in psoriasis.