Drug-induced suppression of phosphorylase kinase activity correlates with resolution of psoriasis as assessed by clinical, histological and immunohistochemical parameters

Background Phosphorylase kinase (PhK), also known as adenosine triphosphate (ATP)-phosphorylase b phosphotransferase, integrates multiple calcium/calm odulin-dependent signalling pathways, including those involved in cell migr ation and cell proliferation, while coupling these pathways to glycogenolys is and ATP-dependent phosphorylation, thus ensuring continuing energy suppl y for these activities. Objectives Our laboratory recently reported correlation of elevated PhK act ivity with psoriatic activity. This study further evaluates the significanc e 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 D-3 analogue and an indirect inhibitor of PhK; (iii) curcumin (di feruloylmethane), a selective PhK inhibitor; and (iv) 10 normal non-psoriat ic subjects. Results PhK activity in units mg(-1) protein was highest in ac tive untreated psoriasis (1204 +/- 804.3; mean +/- SD), lower in the calcip otriol-treated group (550.7 +/- 192.9), lower in curcumin-treated group (20 7.2 +/- 97.6), and lowest in normal skin (105.4 +/- 44.6). One-way analysis of variance performed on log-transformed PhK activity measure showed signi ficant differences among the four groups, F-3,F-36 = 48.79, P < 0.0001. Dec reased PhK activity in curcumin-and calcipotriol-treated psoriasis was asso ciated with corresponding decreases in keratinocyte transferrin receptor (T RR) expression, severity of parakeratosis and density of epidermal CD8+ T c ells. Conclusions Our results demonstrate that drug-induced suppression of PhK ac tivity is associated with resolution of psoriatic activity as assessed by c linical, histological and immunohistochemical criteria, and support the hyp othesis that effective antipsoriatic activity may be achieved through modul ation of PhK activity.