Differential Expression of Protein Kinase C Isoenzymes in Normal and Psoriatic Adult Human Skin: Reduced Expression of Protein Kinase C-βII in Psoriasis Academic Article uri icon

abstract

  • Psoriatic lesions contain elevated levels of 1,2-diacylglycerol,-the physiologic activator of protein kinase C (PKC), suggesting that PKC activation may be aberrant in psoriasis. We therefore have investigated the expression and properties of PKC isozymes in normal and psoriatic skin and in human skin cells. Chromatographic and immunoblot analyses revealed the presence of the calcium-dependent PKC isozymes PKC-α and-β, but not-γ, in normal human epidermis. PKC-β was more prominent, constituting two thirds of the total calcium-dependent PKC activity. In psoriatic lesions, expression of both PKC-α and-β was decreased, with preferential reduction (80%) of PKC-β. Northern analysis and semi-quantitative polymerase chain reaction (PCR) indicated no change in the mRNA levels of PKC-α and-β between normal and psoriatic epidermis. In normal epidermis, PKC-α was expressed mainly in the lower epidermis, whereas PKC-β was localized to the upper cell layers, with very intense staining of CD1a+ Langerhans cells. In psoriasis, PKC-α staining was present in the lower epidermis, whereas PKC-β staining was essentially absent, with the exception of some positive inflammatory cells. In addition to PKC-α and β, immunoblot and Northern/PCR analysis revealed expression of four calcium-independent PKC isozymes,δ, ϵ, ζ and η, in both normal and psoriatic skin. There were no significant differences in mRNA levels among any of these PKC isozymes, between normal and psoriatic skin. Soluble PKC-ζ protein was modestly increased (twofold) in psoriatic, compared to normal, skin, whereas the levels of PKC-δ, ϵ, and η were unchanged. Analysis of PKC isozyme expression in the three major cell types of human epidermis revealed that Langerhans cells and keratinocytes were the major sources of PKC-β and PKC-ζ, respectively. These data demonstrate the diversity of PKC isozyme expression in human skin, and suggest that alterations of PKC-β and-ζ may participate in the aberrant regulation of growth and differentiation observed in psoriasis.

publication date

  • January 1, 1993