Overexpression of tumour necrosis factor-α-converting enzyme in psoriasis

Background Tumour necrosis factor (TNF)-α-converting enzyme (TACE) is a metalloproteinase-disintegrin that releases soluble TNF-α from cells by cleaving within the extracellular domain of membrane-bound pro-TNF-α. It was proposed that TNF-α is involved in the pathogenesis of psoriasis, and it is therefore suggested that TACE has important roles in psoriasis. However, it is unclear whether TACE is expressed in psoriatic tissue. Objectives To clarify whether TACE is expressed in psoriatic lesions and whether expression levels of TACE mRNA are increased in lesional compared with nonlesional psoriatic skin. Methods Skin biopsies were obtained from patients with psoriasis. We examined the expression of TACE in psoriatic tissues using a novel real-time quantitative reverse transcriptase-polymerase chain reaction method and immunohistochemical analysis. Results There was a significant rise in the level of TACE mRNA expression in lesional psoriatic skin compared with nonlesional skin in all patients. There was a statistically significant rise in the level of TACE mRNA expression in lesional psoriatic skin compared with nonlesional skin (mean ± SD TACE/glyceraldehyde-3-phosphate dehydrogenase ratio 0.031 ± 0.012 vs. 0.009 ± 0.002, P < 0.05). In lesional psoriatic skin, immunostaining with anti-TACE antibody was present throughout all layers of the epidermis. TACE immunostaining was found in the cytoplasm of keratinocytes. There was staining associated with blood vessels in the papillary dermis and perivascular inflammatory cells. In particular, mast cells showed strong staining. They contained numerous granules that were stained for TACE in the cytoplasm. Conclusions The findings of the present study suggest that elevation of TACE mRNA in psoriatic lesions is due to many cells, particularly mast cells, that function in lesional psoriatic skin as an important source of TNF-α and other cytokines.