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. Ca²⁺‐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.