Expression of bleomycin hydrolase in keratinization disorders.

A neutral cysteine protease, bleomycin hydrolase (BH), is widely expressed in mammalian tissues, with the skin seeming to contain the highest level. Our previous study revealed that BH transcription is modulated both during differentiation and by cytokines. However, BH involvement in keratinization disorder is not well known. In the present study, we performed immunohistochemical studies of BH and other serine/cysteine proteases in human normal skin and lesional skin with keratinization disorders. BH-positive cells were detected in granular layers of orthokeratotic and hyperkeratotic skin diseases, such as erythrokeratoderma and lichen planus. In parakeratotic skin diseases with porokeratosis, pityriasis rubra pilaris and psoriasis, BH staining was decreased in lesional skins compared to that in normal skin. Similar results were obtained for cysteine proteases, caspase-14 and calpain I. On the other hand, cells positive for serine proteases kallikrein 5 and 7 were increased in parakeratotic and inflammatory skin diseases, such as psoriasis. Semi-quantification analysis revealed that BH- and caspase-14-positive staining had higher intensity than those of the other proteases in normal epidermis. As BH is the major citrulline aminopeptidase in normal granular layer, the alternation would have a significant effect on terminal differentiation processes, such as aberrant processing of deiminated peptides. Therefore, BH may play an important role during the late stage of epidermal differentiation.