BACKGROUND: Phosphorylase kinase (PhK), also known as adenosine
triphosphate (ATP)-phosphorylase b phosphotransferase, integrates
multiple calcium/calmodulin-dependent signalling pathways, including
those involved in cell migration and cell proliferation, while coupling
these pathways to glycogenolysis and ATP-dependent phosphorylation,
thus ensuring continuing energy supply for these activities.

OBJECTIVES: Our laboratory recently reported correlation of elevated
PhK activity with psoriatic activity. This study further evaluates the
significance of drug-induced suppression of PhK activity on psoriatic
activity.

PATIENTS AND METHODS: PhK activity was assayed in four
groups, each with 10 patients: (i) active untreated psoriasis; (ii)
resolving psoriasis treated by calcipotriol (Dovonex(R), Bristol Myers
Squibb, Princeton, NJ, U.S.A. ), a vitamin D3 analogue and an indirect
inhibitor of PhK; (iii) curcumin (diferuloylmethane), a selective PhK
inhibitor; and (iv) 10 normal non-psoriatic subjects.

RESULTS: PhK
activity in units mg-1 protein was highest in active untreated
psoriasis (1204 +/- 804.3; mean +/- SD), lower in the
calcipotriol-treated group (550.7 +/- 192. 9), lower in
curcumin-treated group (207.2 +/- 97.6), and lowest in normal skin
(105.4 +/- 44.6). One-way analysis of variance performed on
log-transformed PhK activity measure showed significant differences
among the four groups, F3,36 = 48.79, P < 0.0001. Decreased PhK
activity in curcumin-and calcipotriol-treated psoriasis was associated
with corresponding decreases in keratinocyte transferrin receptor (TRR)
expression, severity of parakeratosis and density of epidermal CD8+ T
cells.

CONCLUSIONS: Our results demonstrate that drug-induced
suppression of PhK activity is associated with resolution of psoriatic
activity as assessed by clinical, histological and immunohistochemical
criteria, and support the hypothesis that effective antipsoriatic
activity may be achieved through modulation of PhK activity.