DOWN-REGULATION OF LANGERHANS CELL PROTEIN-KINASE C-BETA ISOENZYME EXPRESSION IN INFLAMMATORY AND HYPERPLASTIC DERMATOSES

The family of protein kinase C (PKC) isoenzymes plays a fundamental pa rt in signal transduction, and thereby regulates important cellular fu nctions, including growth, differentiation, cytokine production and ad hesion molecule expression, In lesional psoriatic skin, Ca2+-dependent PKC activity, PKC-beta protein and epidermal Langerhans cell (LC) PKC -beta immunostaining are significantly decreased, indicating activatio n and subsequent down-regulation of PKC, Whether these changes occur i n other inflammatory/hyperplastic dermatoses is, however, unknown. We examined PKC-alpha and PKC-beta expression in normal skin, psoriasis, cutaneous T-cell lymphoma (CTCL), lamellar ichthyosis, non-bullous ich thyosiform erythroderma, atopic dermatitis, urushiol-induced allergic contact dermatitis, and sodium lauryl sulphate (SLS)-induced irritant contact dermatitis, Cryostat sections were stained for PKC-alpha and P KC-beta, and the LC marker CD1a, using an immunoperoxidase technique a nd specific monoclonal antibodies.Double-labelling studies, in normal skin, revealed co-expression of PKC-beta and CD1a by epidermal LCs, An alysis of the number of PKC-beta(+) and CD1a(+) epidermal LCs, in dise ased compared with normal skin, revealed three categories: (i) in psor iasis and CTCL, the PKC-beta(+) epidermal LC number was significantly reduced, whereas the CD1a(+) epidermal LC number was unchanged; (ii) i n allergic and irritant contact dermatitis, both PKC-beta(+) and CD1a( +) epidermal LCs were significantly reduced in number; and (iii) in at opic dermatitis, the PKC-beta(+) epidermal LC number was normal, and C D1a(+) epidermal LCs were significantly increased in number, Moreover, the ratio of epidermal LC PKC+/CD1a(+) was reduced in all the dermato ses studied, suggesting activation of PKC-beta, with subsequent down-r egulation. Within the dermis, increased PKC-beta staining of infiltrat ing cells was observed in all the conditions' studied except lamellar ichthyosis and non-bullous ichthyosiform erythroderma. These data indi cate that: (i) downregulation of LC PKC-beta occurs in a variety of in flammatory and hyperplastic skin disorders, and is not unique to psori asis, and (ii) the pattern of epidermal LC PKC-beta and CD1a expressio n varies among the diseases studied, In mice, PKC activation induces L C migration, Thus, downregulation of epidermal LC PKC-beta associated with reduced CD1a(+) epidermal LCs in allergic and irritant contact de rmatitis suggests that PKC-beta may transduce the signal for migration of LCs from human epidermis.