Funding sources The work has been funded by the Special Account for Research of the University of Crete.
CLINICAL AND LABORATORY INVESTIGATIONS
Infliximab restores the balance between pro- and anti-apoptotic proteins in regressing psoriatic lesions
Article first published online: 9 JAN 2012
© 2011 The Authors. BJD © 2011 British Association of Dermatologists 2011
British Journal of Dermatology
Volume 166, Issue 3, pages 491–497, March 2012
How to Cite
Kokolakis, G., Giannikaki, E., Stathopoulos, E., Avramidis, G., Tosca, A.D. and Krüger-Krasagakis, S. (2012), Infliximab restores the balance between pro- and anti-apoptotic proteins in regressing psoriatic lesions. British Journal of Dermatology, 166: 491–497. doi: 10.1111/j.1365-2133.2011.10689.x
Conflicts of interest None declared.
- Issue published online: 22 FEB 2012
- Article first published online: 9 JAN 2012
- Accepted manuscript online: 10 OCT 2011 07:39AM EST
- Accepted for publication 25 September 2011
- caspase independent;
Background 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.
Objectives To elucidate this finding further, we investigated the epidermal expression of proteins involved in the mitochondria-dependent (intrinsic) pathway of cell death.
Methods 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.
Results 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.
Conclusions 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.