Modulation of cathepsin G expression in severe atopic dermatitis following medium-dose UVA1 phototherapy

Abstract

Background: During the last decade, medium-dose UVA1 phototherapy (50 J/cm2) has achieved great value within the treatment of severe atopic dermatitis (AD). The purpose of our study was to investigate to what extent UVA1 irradiation is able to modulate the status of protease activity by the use of a monoclonal antibody labeling cathepsin G.

Methods: In order to further elucidate the mechanisms by which medium-dose UVA1 irradiation leads to an improvement of skin status in patients with AD, biopsy specimens from 15 patients before and after treatment were analyzed immunohistochemically for proteolytic activation.

Results: Compared to lesional skin of patients with AD before UVA1 irradiation, the number of cells positive for cathepsin G within the dermal infiltrate decreased significantly after treatment. The decrease of cathepsin G+ cells was closely linked to a substantial clinical improvement in skin condition.

Conclusions: In summary, our findings demonstrated that medium-dose UVA1 irradiation leads to a modulation of the expression of cathepsin G in the dermal inflammatory infiltrate in patients with severe AD. Cathepsin G may attack laminin, proteoglycans, collagen I and insoluble fibronectin, to provoke proinflammatory events, to degrade the basement membrane, to destroy the tissue inhibitor of metalloproteinases and to increase the endothelial permeability. Therefore, its down-regulation by UVA1 phototherapy may induce the reduction of skin inflammation as well as improvement of the skin condition.

Figure 1

Pre- and posttherapeutic labeling of cathepsin G in a representative patient with atopic dermatitis Cathepsin G immunostaining in skin biopsies of a representative patient with severe atopic dermatitis before (a) and after (b) treatment. Note the decrease of cathepsin G⁺ inflammatory cells (b) after 3 weeks of medium-dose UVA1 phototherapy with a cumulative dose of 750 J/cm² (original magnification, × 200).

Figure 2

Pre- and posttherapeutic changes of dermal cathepsin G expression Boxplot diagram of the differences between pre- and posttherapeutic percentages of cathepsin G⁺ cells in patients with severe atopic dermatitis (n = 15) following medium-dose UVA1 phototherapy. Black bar = median, whisker = range, triangles = outliers.