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Evaluation of changes in expression pattern of oxidative stress genes under the influence of adalimumab
Beniamin Oskar Grabarek1,2,3, Dominika Wcisło-Dziadecka4, Adrianna Sanakiewicz3
1Center of Oncology, M. Sklodowska-Curie Memorial Institute, Cracow Branch, Warsaw, Poland.
Abstract:
The psoriasis therapy consists of the inhibition of cytokines involved in inducing and development of this disease. The aim of the study was to evaluate the changes in the expression of genes related to the oxidative stress phenomenon in the culture of normal human dermal fibroblasts of Normal Human Dermal Fibroblasts (NHDF) exposed to adalimumab. NHDF culture was exposed to adalimumab for 2-, 8-, and 24-hr periods. The control consisted of the same cells not exposed to adalimumab. The oligonucleotide microarrays HG-U133A 2.0 were used to analyze the changes in gene expression in NHDF culture. Analysis showed that there are 3,881 ID mRNA involved in the induction and development of oxidative stress, the expression of which changes significantly due to the exposure of NHDF cells to adalimumab (p < .05) among 1,369 ID mRNA of them. These include genes associated with apoptosis, the p38 MAPK pathway and the PDGF pathway, and above all with pathways not yet classified. Studies have shown that two genes: NR4A2 and IL1RN, whose expression has changed the most, expressed as Fold Change (FC) seem to be the most promising molecular markers to monitor therapy and loss of cell sensitivity to treatment.
Insights
Adalimumab treatment for psoriasis alters oxidative stress gene expression in normal human dermal fibroblasts. NR4A2 and IL1RN gene expression changes may serve as key markers for monitoring therapy effectiveness and cell sensitivity.
Area of Science:
- Dermatology
- Molecular Biology
- Genomics
Background:
- Psoriasis therapy targets cytokines driving disease development.
- Understanding molecular changes in skin cells during treatment is crucial.
Purpose of the Study:
- To evaluate gene expression changes related to oxidative stress in normal human dermal fibroblasts (NHDF) upon exposure to adalimumab.
- To identify potential molecular markers for monitoring adalimumab therapy in psoriasis.
Main Methods:
- Normal human dermal fibroblasts (NHDF) were exposed to adalimumab for 2, 8, and 24 hours.
- Oligonucleotide microarrays (HG-U133A 2.0) were used to analyze gene expression.
- Gene expression changes were compared between treated and untreated (control) NHDF cultures.
Main Results:
- Significant changes (p < .05) in the expression of 1,369 out of 3,881 oxidative stress-related mRNAs were observed in NHDF cells treated with adalimumab.
- Affected pathways include apoptosis, p38 MAPK, and PDGF signaling.
- The genes NR4A2 and IL1RN showed the most significant expression changes (Fold Change).
Conclusions:
- Adalimumab significantly impacts oxidative stress pathways in dermal fibroblasts.
- NR4A2 and IL1RN are promising molecular markers for assessing adalimumab therapy response and potential loss of cell sensitivity in psoriasis treatment.
