Dahten A, Mergemeier S, Worm M
Department of Dermatology and Allergy, Allergy-Center-Charité Campus Mitte Universitätsmedizin Berlin, Germany.
Allergy. 2007 Aug;62(8):926-33. doi: 10.1111/j.1398-9995.2007.01444.x.
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.
近期研究指出过氧化物酶体增殖物激活受体γ（PPARγ）在炎症免疫反应中的病理生理作用。我们已经表明，特定配体激活PPARγ可通过单核细胞和淋巴细胞减弱过敏性免疫反应。本研究的目的是分析PPARγ的表达及其受炎性细胞因子的调控情况。
我们通过免疫组织化学检查了特应性患者皮损和非皮损皮肤中PPARγ的表达。通过定量实时RT-PCR研究了特应性和非特应性供体外周血单个核细胞以及细胞因子刺激群体中PPARγ mRNA及其亚型的表达模式。
我们的数据显示，特应性皮炎患者皮损皮肤中PPARγ表达增加。对PPARγ mRNA的分析显示，特应性皮炎患者单核细胞和CD4(+) T细胞中PPARγ1的表达显著上调，而PPARγ2的表达未上调。此外，我们证明，调节双相特应性免疫反应的Th细胞因子，如IL-4、IL-13和IFNγ，直接调节PPARγ1的表达。
综上所述，这些数据表明PPARγ亚型在局部细胞因子环境中的表达和调控存在差异。PPARγ1受体表达增加对于基于PPARγ配体治疗特应性皮炎是否有益，目前正在研究中。
