Changes in mRNA expression precede changes in microRNA expression in lesional psoriatic skin during treatment with
L Raaby1, A Langkilde1, R B Kjellerup1
1Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
Background:
Tumour necrosis factor (TNF)-α inhibition is an effective treatment for moderate to severe plaque-type psoriasis. A change in the cytokine expression profile occurs in the skin after 4 days of treatment, preceding any clinical or histological improvements. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression, but miRNA expression has never been studied in psoriatic skin during treatment.
Objective:
To investigate changes in miRNA expression in psoriatic skin during adalimumab treatment and to compare results with changes in miRNA expression in a mouse model of Aldara-induced psoriasis-like skin inflammation.
Methods:
Punch biopsies were obtained from nonlesional and lesional psoriatic skin during adalimumab treatment. In the mouse model of Aldara-induced skin inflammation, biopsies were obtained from TNF-α knockout (KO), IL-17A KO and wild-type mice. miRNA expression levels were analysed with microarray, reverse transcriptase quantitative polymerase chain reaction and in situ hybridization.
Results:
In psoriatic skin, no changes in miRNA expression were seen 4 days after treatment initiation. After 14 days of treatment, the expression of several miRNAs was normalized towards the level seen in nonlesional skin before treatment. miR-23b expression increased after 14 days of treatment and remained high for 84 days, despite unaltered levels at baseline. In the mouse model of Aldara-induced skin inflammation, the level of miR-146a increased, whereas no regulation was seen for miR-203, miR-214-3p, miR-125a, miR-23b or let-7d-5p.
Conclusions:
This study demonstrates that the changes seen in the cytokine expression levels after 4 days of treatment with adalimumab are not facilitated by early changes in miRNA expression.
Insights
Tumour necrosis factor (TNF)-α inhibition for psoriasis does not involve early microRNA (miRNA) expression changes. While cytokine profiles shift within 4 days, significant miRNA alterations in psoriatic skin appear later, around 14 days post-treatment initiation.
Area of Science:
- Dermatology
- Molecular Biology
- Immunology
Background:
- Psoriasis treatment with TNF-α inhibitors shows early cytokine profile changes.
- MicroRNAs (miRNAs) regulate gene expression but their role in psoriasis treatment is unstudied.
- Early cytokine shifts precede clinical improvements in psoriasis treatment.
Purpose of the Study:
- Investigate miRNA expression changes in psoriatic skin during adalimumab treatment.
- Compare these changes to a mouse model of Aldara-induced skin inflammation.
- Determine if early cytokine changes are mediated by miRNA expression.
Main Methods:
- Collected punch biopsies from psoriatic skin (lesional and nonlesional) during adalimumab therapy.
- Analyzed miRNA expression using microarray, RT-qPCR, and in situ hybridization.
- Utilized TNF-α and IL-17A knockout mice in an Aldara-induced psoriasis model.
Main Results:
- No miRNA expression changes observed at 4 days of adalimumab treatment.
- MiRNA expression normalized in psoriatic skin by 14 days of treatment.
- miR-23b expression increased after 14 days and remained elevated; miR-146a increased in the mouse model.
Conclusions:
- Early cytokine expression changes during adalimumab treatment are not driven by immediate miRNA alterations.
- MiRNA expression changes occur later in the treatment response.
- The study provides insights into the molecular mechanisms of psoriasis treatment.
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