The role of peroxisome proliferator-activated receptors (PPARγ) in psoriasis

Background: Peroxisome proliferator–activated receptor γ ( PPARγ) is a nuclear hormone receptor and its activation regulates glucose and lipid metabolism, cell proliferation, differentiation as well as downmodulates the synthesis of pro-inflammatory cytokines. Our previous in vitro study demonstrated the ability of a new PPAR agonist (GED) to suppress proliferative and inflammatory processes in keratinocytes. However, the expression of PPARγ in the hyperproliferative psoriatic epidermis is controversial. The aim of this study is to evaluate the expression of PPARγ in psoriatic skin as compared to healthy epidermis. Materials and Methods: We evaluated the immunohistochemical expression of PPARγ in 13 biopsies of lesional psoriatic skin and 10 biopsies of healthy skin. We further analyse the expression of a proliferation (ki-67) and of an inflammatory (CD3) marker to show possible correlations. Results: In healthy skin PPARγ resulted expressed in the nuclei of the keratinocytes of the stratum granulosum in correlation with the process of differentiation. In psoriatic plaque PPARγ had a cytoplasmic localization in all the suprabasal layers in correlation with proliferative and inflammatory markers. Conclusion: the cytoplasmic localization of PPARγ may indicate a loss of function of the nuclear receptor, supporting the need for a new PPARgamma agonist in the treatment of psoriasis. Phase I study with topical application of GED in psoriatic patients showed absence of side effects.