PMID- 20633014
OWN - NLM
STAT- MEDLINE
DCOM- 20110110
LR  - 20220330
IS  - 1365-2133 (Electronic)
IS  - 0007-0963 (Linking)
VI  - 163
IP  - 5
DP  - 2010 Nov
TI  - The role of endothelial cell apoptosis in the effect of etanercept in psoriasis.
PG  - 928-34
LID - 10.1111/j.1365-2133.2010.09935.x [doi]
AB  - BACKGROUND: Psoriasis is a chronic inflammatory skin disease associated with 
      abnormal vascular expansion in the papillary dermis. Tumour necrosis factor 
      (TNF)-alpha 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-alpha agent etanercept on the expression of 
      endothelial nuclear factor-kappaB (NF-kappaB), 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-kappaB, 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-kappaB, 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.
CI  - (c) 2010 The Authors. BJD (c) 2010 British Association of Dermatologists.
FAU - Avramidis, G
AU  - Avramidis G
AD  - Department of Dermatology, University General Hospital of Heraklion, GR-71110 
      Heraklion-Crete, Greece. avramidis@edu.med.uoc.gr
FAU - Kruger-Krasagakis, S
AU  - Kruger-Krasagakis S
FAU - Krasagakis, K
AU  - Krasagakis K
FAU - Fragiadaki, I
AU  - Fragiadaki I
FAU - Kokolakis, G
AU  - Kokolakis G
FAU - Tosca, A
AU  - Tosca A
LA  - eng
PT  - Journal Article
PL  - England
TA  - Br J Dermatol
JT  - The British journal of dermatology
JID - 0004041
RN  - 0 (BCL2L1 protein, human)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Immunologic Factors)
RN  - 0 (NF-kappa B)
RN  - 0 (Platelet Endothelial Cell Adhesion Molecule-1)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Thrombospondin 1)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (bcl-X Protein)
RN  - OP401G7OJC (Etanercept)
SB  - IM
MH  - Adult
MH  - Apoptosis/*drug effects
MH  - Biopsy
MH  - Endothelial Cells/*drug effects/metabolism
MH  - Etanercept
MH  - Female
MH  - Humans
MH  - Immunoglobulin G/*pharmacology
MH  - Immunohistochemistry
MH  - Immunologic Factors/*pharmacology
MH  - Male
MH  - Middle Aged
MH  - NF-kappa B/metabolism
MH  - Platelet Endothelial Cell Adhesion Molecule-1/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Psoriasis/*drug therapy/metabolism/pathology
MH  - Receptors, Tumor Necrosis Factor
MH  - Thrombospondin 1/metabolism
MH  - Vascular Endothelial Growth Factor A/metabolism
MH  - bcl-X Protein/metabolism
EDAT- 2010/07/17 06:00
MHDA- 2011/01/11 06:00
CRDT- 2010/07/17 06:00
PHST- 2010/07/17 06:00 [entrez]
PHST- 2010/07/17 06:00 [pubmed]
PHST- 2011/01/11 06:00 [medline]
AID - BJD9935 [pii]
AID - 10.1111/j.1365-2133.2010.09935.x [doi]
PST - ppublish
SO  - Br J Dermatol. 2010 Nov;163(5):928-34. doi: 10.1111/j.1365-2133.2010.09935.x.