Peroxisome Proliferator-Activated Receptor-Gamma Is Expressed by Rat Peritoneal Mesothelial Cells: Its Potential Role in Peritoneal Cavity Local Defense
Peroxisome Proliferator-Activated Receptor-Gamma Is Expressed by Rat Peritoneal Mesothelial Cells: Its Potential Role in Peritoneal Cavity Local Defense
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DOI：
10.1159/000098149
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发表时间：
2007-01
影响因子：
4.2
通讯作者：
Yun Zhang;X. Yang;Y. Zhang;Y. Sun;Xun-liang Zou;Q. Kong;Xiu-qing Dong;X. Ye;Xue-Qing Yu
中科院分区：
文献类型：
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作者：
Yun Zhang;X. Yang;Y. Zhang;Y. Sun;Xun-liang Zou;Q. Kong;Xiu-qing Dong;X. Ye;Xue-Qing Yu
背景/目的：腹膜间皮细胞(PMC)在腹膜炎症和免疫反应中发挥重要作用。有报道称，过氧化体增殖物激活受体-γ(PPARγ)配体能有效地减轻炎症过程。然而，PPARγ在PMC中的表达和功能尚未见报道。本研究旨在探讨PPARγ在大鼠肺小管上皮细胞中的表达，以及PPARγ活化对内毒素诱导的巨噬细胞产生CD40和ICAM-1的影响。方法：从SD大鼠的腹膜腔中获取大鼠骨髓基质细胞(RPMCs)，并在一定的体外培养条件下培养。在不同时间点分别用脂多糖、15d-PGJ2和齐格列酮处理细胞。用RT-PCR法和Western印迹法分别检测PPARγ、CD40mRNA和蛋白的表达。免疫细胞化学方法检测PPARγ在细胞内的分布。结果：RPMCs在基因和蛋白水平均表达PPARγ。PPARγ的特异性信号主要定位于胞核，胞浆表达较弱。脂多糖刺激RPMCs后，PPARγ的表达呈时间依赖性增加，3h达高峰，12h达高峰，此后PPARγ表达逐渐减弱。内毒素刺激后CD40、ICAM-1的mRNA表达及ICAM-1的蛋白表达均显著上调。15d-PGJ2和西格列酮均可降低CD40mRNA和ICAM-1蛋白的表达。然而，齐格列酮的疗效不如15d-PGJ2。结论：培养的RPMCs中存在PPARγ的组成性表达，PPARγ配体可强烈抑制脂多糖诱导的RPMCs产生CD40和ICAM-1。提示PPARγ可能通过下调炎性介质参与腹膜局部防御，对腹膜炎所致腹膜纤维化有潜在的预防作用。还需要进一步的体内研究来证明长期效果。
Background/Aims: Peritoneal mesothelial cells (PMCs) play an important role in peritoneal inflammatory and immune response. It was reported that the peroxisomal proliferator-activated receptor-γ (PPARγ) ligand could effectively reduce inflammatory processes. However, the expression and function of PPARγ in PMCs has not been reported. This study was to investigate the expression of PPARγ in rat PMCs and the effect of PPARγ activation on the production of CD40 and ICAM-1 induced by lipopolysaccharide (LPS). Methods: Rat PMCs (RPMCs) were harvested from the peritoneal cavity of Sprague-Dawley rats and maintained under defined in vitro conditions. The cells were treated separately with LPS, 15d-PGJ2, and ciglitazone at different time points. The mRNA and protein expression of PPARγ, CD40 and ICAM-1 were detected by RT-PCR and Western blot, respectively. The intracellular distribution of PPARγ was detected by immunocytochemistry. Results: RPMCs expressed PPARγ both at the mRNA and protein level. The specific signals for PPARγ were mainly localized in the nucleus with weak staining in the cytoplasm. Stimulation of RPMCs with LPS resulted in a time-dependent increase in the expression of PPARγ with the peak of mRNA at 3 h and protein at 12 h. Thereafter the expression of PPARγ gradually attenuated. The mRNA expressions for CD40, ICAM-1 and protein expression of ICAM-1 were significantly upregulated following stimulation with LPS. Both 15d-PGJ2 and ciglitazone decreased the expression of CD40 mRNA and ICAM-1 protein. However, ciglitazone was less effective than 15d-PGJ2. Conclusions: There is constitutive expression of PPARγ in cultured RPMCs and PPARγ ligands which strongly inhibit LPS-induced CD40 and ICAM-1 production in RPMCs. It suggested that PPARγ might play a part in the local defense of the peritoneal cavity by downregulating inflammatory mediators, which may play a potential role in preventing peritoneal fibrosis induced by peritonitis. Further in vivo study is needed to demonstrate the long-term effects.