PPARgamma expression profile and its cytokine driven regulation in atopic dermatitis

Recent studies point to the pathophysiological role of the peroxisome proliferators-activated receptor gamma (PPARgamma) in the inflammatory immune response. We have showed that activation of PPARgamma by specific ligands attenuates the allergic immune response via monocytes and lymphocytes. The objective of this study was to analyse the PPARgamma expression and its regulation via inflammatory cytokines.

We examined the PPARgamma expression in the lesional and nonlesional skin of atopic patients by immunohistochemistry. The expression patterns of PPARgamma mRNA and its isoforms were investigated in peripheral mononuclear blood cells of atopic and nonatopic donors and in cytokine-stimulated populations by quantitative real-time RT-PCR.

Our data show an increased PPARgamma expression in lesional skin from atopic dermatitis patients. The analysis of PPARgamma mRNA reveals a significantly up-regulated expression of PPARgamma1 but not of PPARgamma2 in monocytes and CD4(+) T-cells from atopic dermatitis patients. Furthermore, we demonstrate that Th-cytokines, like IL-4, IL-13 and IFNgamma, which regulate the biphasic atopic immune response, directly regulate the expression of PPARgamma1.

Taken together, these data demonstrate that PPARgamma isoforms are differently expressed and regulated by the local cytokine-milieu. Whether the increased expression of the PPARgamma1 receptor may be beneficial or not for a PPARgamma ligand-based treatment of atopic dermatitis, is currently under investigation.