Expression of bleomycin hydrolase in keratinization disorders

Abstract

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.

Filaggrin – revisited

“…Given its ability to release citrulline from small peptides, it is likely to work in concert with Caspase 14. The decreased levels of expression in keratinization disorders such as AD would be consistent with a reduced ability to process deiminated proteins such as FLG .…”

A pilot study on the use of ultra‐deformable liposomes containing bleomycin in the treatment of equine sarcoid

“…In contrast however, a study by Kamata et al . () in humans identified that concentrations of the enzyme in skin were in fact very high. This contrary finding may confirm that some individuals have more cutaneous enzyme than others.…”

Porokeratosis ptychotropica: a rare and evolving variant of porokeratosis

“…Porokeratosis represents a disorder of epidermal keratinization. Its exact etiology has not been well established but there is increasing evidence that implicate aberrant terminal differentiation of keratinocytes . Porokeratosis is characterized by the cornoid lamella, a column of tightly packed parakeratotic cells that resides within a depression of the epidermis.…”

“…Its exact etiology has not been well established but there is increasing evidence that implicate aberrant terminal differentiation of keratinocytes. 2 Porokeratosis is characterized by the cornoid lamella, a column of tightly packed parakeratotic cells that resides within a depression of the epidermis. The cornoid lamella is seen in all variants of porokeratosis, but it is not pathognomonic for the disorder.…”