Infliximab restores the balance between pro- and anti-apoptotic proteins in regressing psoriatic lesions
| Autor: | G, Kokolakis, E, Giannikaki, E, Stathopoulos, G, Avramidis, A D, Tosca, S, Krüger-Krasagakis |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Keratinocytes Analysis of Variance Tumor Necrosis Factor-alpha Biopsy NF-kappa B Antibodies Monoclonal Apoptosis Inducing Factor Down-Regulation Apoptosis Middle Aged Immunohistochemistry Infliximab Up-Regulation Caspases Humans Psoriasis Dermatologic Agents Epidermis Apoptosis Regulatory Proteins bcl-2-Associated X Protein |
| Zdroj: | The British journal of dermatology. 166(3) |
| ISSN: | 1365-2133 |
| Popis: | Psoriasis and psoriatic arthritis are treated very efficaciously with infliximab, a chimaeric human-murine antitumour necrosis factor (TNF)-α antibody. As we reported earlier, infliximab, besides its anti-inflammatory properties, induces a caspase-independent programmed cell death of psoriatic keratinocytes.To elucidate this finding further, 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 nonlesional 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. These differences in expression correlated with decreases in epidermal thickness and clinical outcome (Psoriasis Area and Severity Index). At day 21, expression levels of apoptosis-related proteins in lesional skin approximated those found in nonlesional skin.Our data therefore suggest that TNF-targeting agents may induce the regression of psoriasis at least in part by normalizing the expression of apoptosis-related proteins in lesional keratinocytes. |
| Databáze: | OpenAIRE |
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