Opposing effects of UVA1 phototherapy on the expression of bcl-2 and p53 in atopic dermatitis.

Recently, medium-dose UVA1 phototherapy (50 J/cm2) has been introduced as an effective treatment for severe atopic dermatitis (AD). In order to further elucidate the mechanisms by which medium-dose UVA1 irradiation leads to an improvement in skin status in patients with AD, biopsy specimens from ten patients before and after treatment were analysed immunohistochemically for features of apoptosis. We sought to determine the extent to which UVA1 irradiation was able to modulate the balance between p53 and bcl-2 expression in vivo using monoclonal antibodies labelling these proteins. As compared with lesional skin of patients with AD before UVA1 irradiation, the number of dermal cells, apparently lymphocytes, that were positive for p53 had significantly increased after treatment and, in addition, some basal keratinocytes showed slight positive staining for p53. An increased expression of the bcl-2 gene before treatment in predominately dermal lymphocytes was significantly downregulated by UVA1 therapy. The increase in p53+ cells and the decrease in bcl-2+ cells were closely linked to a significant reduction in dermal T cells (CD3+) and a substantial clinical improvement in skin condition. In summary, medium-dose UVA1 irradiation led to a marked modulation of the expression of p53 and bcl-2, and this plays a key role in regulating UVA1-induced apoptosis.

UVA1 irradiation induces deoxyribonuclease dependent apoptosis in cutaneous T-cell lymphoma in vivo.

Cutaneous T-cell lymphoma (CTCL) is a malignancy of mature T-cells, predominantly of the helper phenotype, that primarily invade the skin. Different photo- and chemotherapeutic treatments are known to be beneficial in early-stage CTCL. This observation has initiated prospective investigations into the efficacy of phototherapeutic regimens. The purpose of our study was to investigate the ability of medium-dose UVA1 phototherapy (60 J/cm2) to induce apoptosis (programmed cell death) in skin infiltrating T-cells of CTCL in vivo. We describe the results of three different staining methods for formalin-fixed, paraffin-embedded tissue sections. The in situ end-labeling (ISEL) procedure, nuclear staining using the DNA-binding fluorochrome Hoechst 33342, and immunohistochemistry using polyclonal antibodies against recombinant mouse deoxyribonuclease I (DNase I) demonstrated that UVA1 irradiation was able to induce marked apoptosis in CTCL. Thereby, ISEL and Hoechst staining clearly revealed DNA-condensation and nuclear fragmentation, accompanied by the formation of typical "apoptotic bodies". The accumulation of DNase I immunoreactivity in the cytoplasm of lymphocytes in UVA1 irradiated skin indicated that DNase I or DNase I-related endonucleases may have acted as apoptotic endonuclease(s) which were synthesized after UVA1 irradiation prior to their apoptotic elimination.