Abstract
In our previous work, we built the model of PPARγ dependent pathways involved in the development of the psoriatic lesions. Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor and transcription factor which regulates the expression of many proinflammatory genes. We tested the hypothesis that low levels of PPARγ expression promote the development of psoriatic lesions triggering the IL17-related signaling cascade. Skin samples of normally looking and lesional skin donated by psoriasis patients and psoriatic CD3+ Tcells samples (n = 23) and samples of healthy CD3+ T cells donated by volunteers (n = 10) were analyzed by real-time PCR, ELISA and immunohistochemistry analysis. We found that the expression of PPARγ is downregulated in human psoriatic skin and laser treatment restores the expression. The expression of IL17, STAT3, FOXP3, and RORC in psoriatic skin before and after laser treatment were correlated with PPARγ expression according to the reconstructed model of PPARγ pathway in psoriasis.In conclusion, we report that PPARγ weakens the expression of genes that contribute in the development of psoriatic lesion. Our data show that transcriptional regulation of PPARγ expression by FOSL1 and by STAT3/FOSL1 feedback loop may be central in the psoriatic skin and T-cells.
Highlights
We found a significant increase in the expression levels of the following genes—IL17 (42.39 ± 16.68), Signal Transducer and Activator of Transcription 3 (STAT3) (4.42 ± 0.90), RORC (7.68 ± 1.62, and FOSL1 (9.72 ± 4.98)
For the step of validation, we studied the expression of PPARγ, STAT3, IL17A, RORC, FOXP3, and FOSL1 in human psoriatic skin samples and visually healthy skin samples before and after laser treatment
We detected the repression of PPARγ activity in human psoriatic skin and blood immune cells (CD3+ T cells) from 23 patients with real-time PCR method, ELISA and immunohistochemistry analysis
Summary
We analyzed biopsies and peripheral blood samples from patients who were treated in the V G Korolenko Hospital, Moscow Scientific and Practical Centre of Dermatovenerology and Cosmetology. Total were analyzed from 23 patients with plaque-type psoriasis and 10 healthy controls. The diagnoses were confirmed by the pathomorphological examination of skin biopsies. Local anesthesia and dermatological punch (4 mm) were used for the collection of skin samples. Healthy skin samples were taken at a distance of 3 cm from a psoriatic lesion. The research was approved by the Local Ethical Committee at the Center for Theoretical Problems of Physical-Chemical Pharmacology, Russian Academy of Science, and complies with the principles of the Helsinki Declaration. The laser treatment was provided 2–3 times a week. Skin samples were collected before the treatment and one day after the 7th laser seance
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