Down-regulation of Langerhans cell protein kinase C-Β isoenzyme expression in inflammatory and hyperplastic dermatoses

Abstract

The family of protein kinase C (PKC) isoenzymes plays a fundamental part in signal transduction, and thereby regulates important cellular functions, including growth, differentiation, cytokine production and adhesion molecule expression. In lesional psoriatic skin. Ca 2+ -dependent PKC activity, PKC-Β protein and epidermal Langerhans cell (LC) PKC-Β immunostaining are significantly decreased, indicating activation and subsequent down-regulation of PKC. Whether these changes occur in other inflammatory/hyperplastic dermatoses is, however, unknown. We examined PKC-Α and PKC-Β expression in normal skin, psoriasis, cutaneous T-cell lymphoma (CTCL), lamellar ichthyosis, non-bullous ichthyosiform erythroderma, atopic dermatitis, urushiol-induced allergic contact dermatitis, and sodium lauryl sulphate (SLS)-induced irritant contact dermatitis. Cryostat sections were stained for PKC-Α and PKC-Β, and the LC marker CDla, using an immunoperoxidase technique and specific monoclonal antibodies. Double-labelling studies, in normal skin, revealed co-expression of PKC-Β and CDla by epidermal LCs. Analysis of the number of PKC- Β+ and CDl a+ epidermal LCs, in diseased compared with normal skin, revealed three categories: (i) in psoriasis and CTCL. the PKC- Β+ epidermal LC number was significantly reduced, whereas the CDl a+ epidermal LC number was unchanged; (ii) in allergic and irritant contact dermatitis, both PKC-Β+ and CDla + epidermal LCs were significantly reduced in number; and (iii) in atopic dermatitis, the PKC-Β + epidermal LC number was normal, and CDla + epidermal LCs were significantly increased in number. Moreover, the ratio of epidermal LC PKC + /CDla + was reduced in all the dermatoses studied, suggesting activation of PKC-Β, with subsequent down-regulation. Within the dermis, increased PKC-Β staining of infiltrating cells was observed in all the conditions studied except lamellar ichthyosis and non-bullous ichthyosiform erythroderma. These data indicate that: (i) down-regulation of LC FKC-Β occurs in a variety of inflammatory and hyperplastic skin disorders, and is not unique to psoriasis, and (iii the pattern of epidermal LC PKC-Β and CDla expression varies among the diseases studied. In mice, PKC activation induces LC migration. Thus, down-regulation of epidermal LC PKC-Β associated with reduced CDla + epidermal LCs in allergic and irritant contact dermatitis suggests that PK.C-Β may transduce the signal for migration of LCs from human epidermis.