| Infliximab restores the balance between pro- and anti-apoptotic proteins in regressing psoriatic lesions. | |
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MedLine Citation:
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PMID: 21985184 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Psoriasis and psoriatic arthritis are treated very efficaciously with infliximab, a chimaeric human-murine anti-tumor necrosis factor alpha (TNF-α) antibody. As we reported earlier, infliximab, besides its anti-inflammatory properties, induces a caspase-independent programmed cell death of psoriatic keratinocytes. In order to further elucidate this finding, we investigated the epidermal expression of proteins involved in the mitochondria-dependent (intrinsic) pathway of cell death. Quantification of proteins with pro- (p53, AIF, Bax) and anti-apoptotic functions (Bcl-2, Bcl-XL) and of NF-κB was performed by means of immunohistochemistry and digital image analysis of the staining of non-lesional skin and lesional psoriatic skin from patients treated with infliximab at weeks 0, 2, and 6. Serial biopsies from psoriatic plaques of samples taken at days 0, 5, 14, and 21 of therapy demonstrated a significant downregulation of anti-apoptotic proteins Bcl-2, Bcl-XL, and NF-κB during treatment, and, in parallel, a significant upregulation of pro-apoptotic proteins p53, Bax, and AIF, which correlated with decreases in epidermal thickness and clinical outcome (PASI). At day 21, expression levels of apoptosis-related proteins in lesional skin approximated those found in non-lesional skin. Our data therefore suggest that TNF-targeting agents may induce the regression of psoriasis at least in part by normalizing the expression apoptosis-related proteins in lesional keratinocytes. |
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Authors:
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G Kokolakis; E Giannikaki; E Stathopoulos; G Avramidis; A D Tosca; S Krüger-Krasagakis |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-10-10 |
Journal Detail:
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Title: The British journal of dermatology Volume: - ISSN: 1365-2133 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0004041 Medline TA: Br J Dermatol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 British Association of Dermatologists. |
Affiliation:
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Departments of Dermatology Histopathology, University Hospital of Heraklion, University of Crete, Greece Department of Dermatology, Charité Universitätsmedizin, Berlin, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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