Reverse transcriptase activity in human normal and psoriatic skin samples

Abstract

About half of the human genome is composed of ancient transposable elements that became integrated in the genome throughout the course of evolution by DNA transposition or by retrotransposition. Most of these elements have degenerated. However, a few of them have conserved their coding capacities and could still have a role in physiological and pathological processes. OBJECTIVES To investigate whether reverse transcriptase (RT) of human endogenous retroelements can be expressed at the protein level and can also be functional, and to associate RT expression and activity to a pathological situation, namely psoriasis. Expression of RT proteins was investigated by immunohistochemistry on normal (n = 11), psoriatic (n = 19) and atopic (n = 12) skin sections and by Western blot on normal skin protein extracts. RT activity was measured by a colorimetric method in protein extracts from normal (n = 17) and lesional psoriatic (n = 35) skin. Two assays were performed in each extract: one was optimized for Moloney murine leukaemia virus or mammalian C-type retroviruses, and the other for mouse mammary tumour virus or D-type retroviruses. RT proteins were detected in the uppermost layer of the epidermis and in a few dermal cells of normal skin. The main protein had a molecular weight of 57 kDa. An increased number of RT-positive cells was stained in the psoriatic lesion both within the epidermis and within the dermal compartment. In addition, a massive staining was noted in Munro's abscesses. Finally, RT activities were 2-3 times higher in psoriatic protein extracts than in normal skin protein extracts. Active endogenous retroelements can produce functional RT proteins. In normal skin, we observed RT expression in all samples tested whereas RT activity was barely detectable. In psoriatic samples, the number of RT-positive cells was increased, as was the RT activity. This latter characteristic allowed us to determine a subset of psoriatic samples with an increased Mg(2+) RT activity. These results suggest that a basal level of endogenous retroelement activity exists in normal skin and that keratinocyte hyperproliferation and/or inflammation observed in psoriasis promote this activity. The role of endogenous retroelements in skin physiology and pathology deserves attention.