Iloprost has potent anti-inflammatory properties on human monocyte-derived dendritic cells
Iloprost has potent anti-inflammatory properties on human monocyte-derived dendritic cells
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DOI：
10.1111/j.1365-2222.2010.03558.x
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发表时间：
2010-08-01
影响因子：
6.1
通讯作者：
Idzko, M.
中科院分区：
文献类型：
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作者：
Mueller, T.;Duerk, T.;Idzko, M.
研究背景稳定的前列腺素I2类似物伊洛前列素（iloprost）通过调节骨髓树突状细胞（myeloid dendritic cells，DCs）的功能抑制小鼠过敏性气道炎症，本研究旨在探讨伊洛前列素对人单核细胞来源的DCs的生物学活性。通过ELISA测量DC和CD 4 + T细胞的细胞因子分泌。流式细胞术分析了DC与CD 4 + CD 45 RA + T细胞共培养后转录因子FoxP 3的表达。结果发现人单核细胞来源的DC表达PGI 2受体IP特异性mRNA，伊洛前列素刺激导致未成熟DC（iDC）和成熟DC（mDC）中环AMP水平增加。此外，伊洛前列素剂量依赖性地抑制mDC中TNF-α、IL-6、IL-8和IL-12 p70的分泌，同时其增强IL-10的产生。细胞因子分泌的变化被DC的T细胞引发能力的改变所掩盖：在伊洛前列素处理的mDC和初始CD 45 RA + T细胞的共培养实验中，可以观察到调节性T细胞的诱导，如通过增加的细胞内FoxP 3表达和IL-10产生所证明的。此外，伊洛前列素抑制MIP-3 β诱导的mDCs.ConclusionIn总结，我们的研究结果提供证据表明，伊洛前列素深刻地影响人髓样DCs的功能。因此，伊洛前列素也可能是治疗人类哮喘的一种新的治疗选择。Muller，T.杜克，B。布卢门塔尔，Y. Herouy，S. Sorichter，M. Grimm，E. Panther，S. Cicko，J. Norgauer和M. Idzko，临床与实验过敏，2010（40）1214-1221.
P>BackgroundThe stable prostaglandin I2 analogue (iloprost) iloprost has been shown to inhibit allergic airway inflammation in mice by modulating the function of myeloid dendritic cells (DCs).ObjectiveThe aim of the current study was to investigate the biological activity of iloprost on human monocyte-derived DCs.MethodsI prostanoid (IP) receptor expression was analysed by RT-PCR. Cytokine secretion by DCs and CD4+ T cells was measured by ELISA. The expression of the transcription factor FoxP3 after co-culture of DCs with CD4+ CD45RA+ T cells was analysed by flow cytometry.ResultsHuman monocyte-derived DCs were found to express mRNA specific for the PGI2 receptor IP, and stimulation with iloprost resulted in increased cyclic AMP levels in both immature DCs (iDCs) and mature DCs (mDCs). Moreover, iloprost dose dependently inhibited the secretion of TNF-alpha, IL-6, IL-8 and IL-12p70 in mDCs, while it enhanced IL-10 production. Changes in cytokine secretion were paralleled by an altered T-cell priming capacity of DCs: in co-culture experiments of iloprost-treated mDC and naive CD45RA+ T cells, an induction of regulatory T cells could be observed, as demonstrated by increased intracellular FoxP3 expression and IL-10 production. Additionally, iloprost inhibited the MIP-3 beta-induced migration of mDCs.ConclusionIn summary, our results provide evidence that iloprost profoundly affects the function of human myeloid DCs. Therefore, iloprost might also be a new therapeutical option for the treatment of asthma in humans.Cite this as: T. Muller, T. Durk, B. Blumenthal, Y. Herouy, S. Sorichter, M. Grimm, E. Panther, S. Cicko, J. Norgauer and M. Idzko, Clinical & Experimental Allergy, 2010 (40) 1214-1221.