Cyclophilin Content of Normal and Psoriatic Epidermis

Abstract

The unique, immunosuppressive agent cyclosporine A has been shown to be of important therapeutic value in the treatment of psoriasis and other inflammatory dermatoses. To investigate the basis for its therapeutic efficacy, the tissue and cellular content of cyclophilin, a cytosolic receptor for cyclosporine A, has been determined in keratome biopsies from normal and psoriatic epidermis and in cultured, adult human keratinocytes. The mean cyclophilin content of normal (n = 10), involved (n = 10), and uninvolved (n = 10) psoriatic epidermal samples was not significantly different (0.126 +/- 0.016, 0.106 +/- 0.009, and 0.153 +/- 0.018 microgram cyclosporine A bound/mg cytosolic protein). Similarly, the cyclophilin content of keratinocytes cultured from normal and psoriatic epidermis (0.21 +/- 0.016 and 0.18 +/- 0.024 microgram/mg protein, respectively) did not differ significantly. Western blot analysis of normal and psoriatic epidermal extracts with monospecific rabbit anti-cyclophilin antisera revealed a single band of 17,000 daltons, which co-migrated with highly purified bovine cyclophilin. The intensity of this band was similar in normal and psoriatic samples, indicating that immunoreactive cyclophilin content was similar. Cyclophilin mRNA was readily detected in normal and involved psoriatic epidermis by RNA blot hybridization, and expression was not significantly different in normal and psoriatic epidermis. These findings indicate that cyclophilin is present in human keratinocytes and epidermis, where it may account for the accumulation of cyclosporine during therapy. However, the similar cyclophilin content of normal and diseased tissue suggests that differences in cyclosporine uptake probably do not account for its therapeutic efficacy in psoriasis.