Analysis of PPARγ Signaling Activity in Psoriasis

In our previous work, we built the model of PPAR gamma dependent pathways involved in the development of the psoriatic lesions. Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a nuclear receptor and transcription factor which regulates the expression of many proinflammatory genes. We tested the hypothesis that low levels of PPAR gamma 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 PPAR gamma 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 PPAR gamma expression according to the reconstructed model of PPAR gamma pathway in psoriasis.In conclusion, we report that PPAR gamma weakens the expression of genes that contribute in the development of psoriatic lesion. Our data show that transcriptional regulation of PPAR gamma expression by FOSL1 and by STAT3/FOSL1 feedback loop may be central in the psoriatic skin and T-cells.

Automated summary

Our study demonstrates the involvement of PPAR-gamma in the development of psoriatic lesions, with laser treatment restoring its expression. The transcriptional regulation of PPAR-gamma is correlated with the expression of genes such as IL17, STAT3, FOXP3, and RORC in psoriatic skin and T cells.