PPARγ expression profile and its cytokine driven regulation in atopic dermatitis

Background: Recent studies point to the pathophysiological role of the peroxisome proliferators‐activated receptor gamma (PPARγ) in the inflammatory immune response. We have showed that activation of PPARγ by specific ligands attenuates the allergic immune response via monocytes and lymphocytes. The objective of this study was to analyse the PPARγ expression and its regulation via inflammatory cytokines. Methods: We examined the PPARγ expression in the lesional and nonlesional skin of atopic patients by immunohistochemistry. The expression patterns of PPARγ 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. Results: Our data show an increased PPARγ expression in lesional skin from atopic dermatitis patients. The analysis of PPARγ mRNA reveals a significantly up‐regulated expression of PPARγ1 but not of PPARγ2 in monocytes and CD4 + T‐cells from atopic dermatitis patients. Furthermore, we demonstrate that Th‐cytokines, like IL‐4, IL‐13 and IFNγ, which regulate the biphasic atopic immune response, directly regulate the expression of PPARγ1. Conclusion: Taken together, these data demonstrate that PPARγ isoforms are differently expressed and regulated by the local cytokine‐milieu. Whether the increased expression of the PPARγ1 receptor may be beneficial or not for a PPARγ ligand‐based treatment of atopic dermatitis, is currently under investigation.