Induction of vitamin D receptor mRNA expression in psoriatic plaques correlates with clinical response to 1,25-dihydroxyvitamin D-3

Psoriasis is a skin disorder characterized by hyperproliferation of epidermal keratinocytes. 1 alpha,25-Dihydroxyvitamin D-3 (1 alpha,25(OH)(2)D-3) and its analogs have been shown to inhibit keratinocyte proliferation in vitro and to be therapeutically effective for the treatment of psoriasis. Some patients with psoriasis, however, do not have a favorable response to 1 alpha,25(OH)(2)D-3 therapy, To evaluate the differential responsiveness to 1 alpha,25(OH)(2)D-3 treatment, we examined the expression of vitamin D receptor mRNA in psoriatic lesions by reverse transcription-polymerase chain reaction using glyceraldehyde-3-phosphate dehydrogenase as an internal control, In this double-blind clinical trial, we recruited 18 patients who received topical treatment of 1 alpha,25(OH)(2)D-3 (15 mu g/g Vaseline) or placebo on separate psoriatic lesions for 8 weeks. In patients who showed >90% clinical improvement of their psoriatic lesions treated with 1 alpha,25(OH)(2)D-3 (n = 9), an increase of 130 +/- 37% in vitamin D receptor mRNA level was observed in 1 alpha,25(OH)(2)D-3-treated lesions when compared with the corresponding placebo controls. There was no increase in vitamin D receptor mRNA level in the lesions treated with this drug in patients who did net respond to the treatment. These data suggest that the antiproliferative activity of 1 alpha,25(OH)(2)D-3 is closely associated with the expression of its cognate receptor.