DIFFERENTIAL EXPRESSION OF PROTEIN-KINASE-C ISOENZYMES IN NORMAL AND PSORIATIC ADULT HUMAN SKIN - REDUCED EXPRESSION OF PROTEIN KINASE-C-BETA-II IN PSORIASIS
Gj. Fisher et al., DIFFERENTIAL EXPRESSION OF PROTEIN-KINASE-C ISOENZYMES IN NORMAL AND PSORIATIC ADULT HUMAN SKIN - REDUCED EXPRESSION OF PROTEIN KINASE-C-BETA-II IN PSORIASIS, Journal of investigative dermatology, 101(4), 1993, pp. 553-559
Psoriatic lesions contain elevated levels of 1,2-diacylglycerol, the p
hysiologic activator of protein kinase C (PKC), suggesting that PKC ac
tivation 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-alpha
and -beta, but not -gamma, in normal human epidermis. PKC-beta was mor
e prominent, constituting two thirds of the total calcium-dependent PK
C activity. In psoriatic lesions, expression of both PKC-alpha and -be
ta was decreased, with preferential reduction (80%) of PKC-beta. North
ern analysis and semi-quantitative polymerase chain reaction (PCR) ind
icated no change in the mRNA levels of PKC-alpha and -beta between nor
mal and psoriatic epidermis. In normal epidermis, PKC-alpha was expres
sed mainly in the lower epidermis, whereas PKC-beta was localized to t
he upper cell layers, with very intense staining of CD1a+ Langerhans c
ells. In psoriasis, PKC-alpha staining was present in the lower epider
mis, whereas PKC-beta staining was essentially absent, with the except
ion of some positive inflammatory cells. In addition to PKC-alpha and
beta, immunoblot and Northern/PCR analysis revealed expression of four
calcium-independent PKC isozymes, delta, epsilon, zeta, and eta, in b
oth normal and psoriatic skin. There were no significant differences i
n mRNA levels among any of these PKC isozymes, between normal and psor
iatic skin. Soluble PKC-zeta protein was modestly increased (twofold)
in psoriatic, compared to normal, skin, whereas the levels of PKC-delt
a, epsilon, and eta were unchanged. Analysis of PKC isozyme expression
in the three major cell types of human epidermis revealed that Langer
hans cells and keratinocytes were the major sources of PKC-beta and PK
C-zeta, respectively. These data demonstrate the diversity of PKC isoz
yme expression in human skin, and suggest that alterations of PKC-beta
and -zeta may participate in the aberrant regulation of growth and di
fferentiation observed in psoriasis.