Downregulation of involucrin in psoriatic lesions following therapy with propylthiouracil, an anti-thyroid thioureylene: immunohistochemistry and gene expression analysis

BackgroundPropylthiouracil (PTU), an anti-thyroid thioureylene, has been shown to be effective in chronic plaque psoriasis. Involucrin is a precursor protein that is upregulated in psoriasis. ObjectivesThis study evaluated the expression of involucrin in the epidermis of skin in psoriatic plaques before and after treatment with PTU. MethodsThis was an open-label, prospective study in which 25 psoriasis patients underwent skin biopsies prior to treatment with oral PTU 100mg three times per day for 12weeks. Patients were assessed at 2, 6, and 12weeks. Skin biopsies were repeated at the same sites at 12weeks. Pre- and post-treatment specimens were subjected to immunohistochemical staining and real-time polymerase chain reaction for involucrin. ResultsMeanstandard deviation (SD) scores on the Psoriasis Area and Severity Index reduced significantly from 17.86 +/- 9.9 at baseline to 4.63 +/- 4.1 at week12 (P<0.001). Histomorphometric analysis revealed marked decreases in numbers of positively stained cells and intensity of staining. Staining became localized to the upper granular layers after therapy. Immunohistochemical scoring for involucrin reduced from a mean +/- SD of 9.00 +/- 0.67 at baseline to 3.90 +/- 0.88 at week12 (P<0.0001). ConclusionsIn psoriasis, there is increased expression of involucrin, which leads to abnormal keratinocyte differentiation and hence to the formation of psoriatic plaques. The therapeutic effect of PTU in psoriasis may be attributable to the downregulation of involucrin. Larger trials should further elucidate the mechanism and therapeutic potential of PTU in psoriasis.