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Pathway Analysis of Skin from Psoriasis Patients after Adalimumab Treatment Reveals New Early Events in the Anti-Inflammatory Mechanism of Anti-TNF-α.
- Source :
-
PloS one [PLoS One] 2016 Dec 22; Vol. 11 (12), pp. e0167437. Date of Electronic Publication: 2016 Dec 22 (Print Publication: 2016). - Publication Year :
- 2016
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Abstract
- Psoriasis is a chronic cutaneous inflammatory disease. The immunopathogenesis is a complex interplay between T cells, dendritic cells and the epidermis in which T cells and dendritic cells maintain skin inflammation. Anti-tumour necrosis factor (anti-TNF)-α agents have been approved for therapeutic use across a range of inflammatory disorders including psoriasis, but the anti-inflammatory mechanisms of anti-TNF-α in lesional psoriatic skin are not fully understood. We investigated early events in skin from psoriasis patients after treatment with anti-TNF-α antibodies by use of bioinformatics tools. We used the Human Gene 1.0 ST Array to analyse gene expression in punch biopsies taken from psoriatic patients before and also 4 and 14 days after initiation of treatment with the anti-TNF-α agent adalimumab. The gene expression was analysed by gene set enrichment analysis using the Functional Annotation Tool from DAVID Bioinformatics Resources. The most enriched pathway was visualised by the Pathview Package on Kyoto Encyclopedia of Genes and Genomes (KEGG) graphs. The analysis revealed new very early events in psoriasis after adalimumab treatment. Some of these events have been described after longer periods of anti-TNF-α treatment when clinical and histological changes appear, suggesting that effects of anti-TNF-α treatment on gene expression appear very early before clinical and histological changes. Combining microarray data on biopsies from psoriasis patients with pathway analysis allowed us to integrate in vitro findings into the identification of mechanisms that may be important in vivo. Furthermore, these results may reflect primary effect of anti-TNF-α treatment in contrast to studies of gene expression changes following clinical and histological changes, which may reflect secondary changes correlated to the healing of the skin.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Adalimumab pharmacology
Adult
Aged
Anti-Inflammatory Agents pharmacology
Cytokines genetics
Cytokines metabolism
Gene Expression drug effects
Hematopoietic Cell Growth Factors genetics
Hematopoietic Cell Growth Factors metabolism
Humans
Middle Aged
Oligonucleotide Array Sequence Analysis
Platelet-Derived Growth Factor genetics
Platelet-Derived Growth Factor metabolism
Principal Component Analysis
Psoriasis genetics
Psoriasis pathology
Receptors, Cytokine genetics
Receptors, Cytokine metabolism
Skin pathology
Time Factors
Adalimumab therapeutic use
Anti-Inflammatory Agents therapeutic use
Psoriasis drug therapy
Skin metabolism
Tumor Necrosis Factor-alpha immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 11
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 28005985
- Full Text :
- https://doi.org/10.1371/journal.pone.0167437