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The role of endothelial cell apoptosis in the effect of etanercept in psoriasis
Author(s) -
Avramidis G.,
KrügerKrasagakis S.,
Krasagakis K.,
Fragiadaki I.,
Kokolakis G.,
Tosca A.
Publication year - 2010
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.1365-2133.2010.09935.x
Subject(s) - cd31 , angiogenesis , medicine , etanercept , tunel assay , vascular endothelial growth factor , psoriasis , terminal deoxynucleotidyl transferase , endothelial stem cell , tumor necrosis factor alpha , vascular endothelial growth factor a , pathology , immunology , cancer research , immunohistochemistry , biology , in vitro , biochemistry , vegf receptors
Summary Background Psoriasis is a chronic inflammatory skin disease associated with abnormal vascular expansion in the papillary dermis. Tumour necrosis factor (TNF)‐α is a proinflammatory cytokine that can induce antiapoptotic proteins and endothelial cell activation factors in psoriasis. Objectives The present study investigated the effect of the anti‐TNF‐α agent etanercept on the expression of endothelial nuclear factor‐κB (NF‐κB), angiogenic vascular endothelial growth factor (VEGF), endothelial cell marker CD31, antiangiogenic factor thrombospondin‐1 (TSP‐1), and antiapoptotic factors Bcl‐2 and Bcl‐xL in psoriasis. Methods Sixteen patients with moderate‐to‐severe psoriasis were included in the study and treated with etanercept 50 mg twice weekly subcutaneously for 12 weeks. Biopsies of lesional skin (baseline, weeks 3, 6 and 10) were obtained and immunohistochemically stained with antibodies for CD31, VEGF, TSP‐1, NF‐κB, Bcl‐2 and Bcl‐xL. Double immunofluorescence staining for VEGF and CD31 was evaluated with confocal laser microscopy. The terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick‐end labelling (TUNEL) assay was applied for apoptosis detection. Results Etanercept caused a statistically significant time‐dependent reduction in the number of dermal blood vessels, the number of CD31+ cells and VEGF in psoriatic lesions, with induction of endothelial cell apoptosis and statistically significant upregulation of TSP‐1 in psoriatic vessels. Immunohistochemical analysis showed significant reduction of NF‐κB, Bcl‐2 and Bcl‐xL expression in endothelial cells during treatment. These changes were accompanied by a marked clinical response. Conclusions The present findings suggest that treatment with etanercept induces apoptosis, reduces apoptosis‐inhibiting factors in psoriatic endothelial cells, and decreases angiogenesis in psoriatic skin.